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Archive for the ‘Pharmaceutical Drug Discovery’ Category


Danny Bar-Zohar, MD –  New R&D Leader for new pipelines at Merck KGaA as Luciano Rossetti steps out

Reporter: Aviva Lev-Ari, PhD, RN

 

Danny Bar-Zohar, MD – A Pharmaceutical Executive Profile in R&D: Ex-Novastis, Ex-Teva

Experience

Education

SOURCE

https://www.linkedin.com/in/danny-bar-zohar-513904a/

 

Novartis vet Danny Bar-Zohar leaps back into R&D, taking over the development team at Merck KGaA as Luciano Rossetti steps out

John Carroll
Editor & Founder

After a brief stint as a biotech investor at Syncona, Novartis vet Danny Bar-Zohar is back in R&D, and he’s taking the lead position at Merck KGaA’s drug division.

Bar-Zohar had led late-stage clinical development across a variety of areas — neuroscience, immunology, oncology and ophthalmology, among others — before joining the migration of talent out of the Basel-based multinational. He had been at Novartis for 7 years, which followed an earlier chapter in research at Teva.

Luciano Rossetti
The scientist is taking the lead on development at Merck KGaA, in place of Luciano Rossetti, who had a mixed record in R&D that nevertheless marked a big improvement over the dismal run the company had endured earlier. Joern-Peter Halle will continue on as global head of research. Rossetti is retiring after 6 years of running the research group, which has extensive operations in Germany as well as Massachusetts.

Their PD-L1 Bavencio — allied with Pfizer — has had a few successes, and a whole slate of failures. Sprifermin was touted as a big potential advance in osteoarthritis, but Merck KGaA is now auctioning off that part of the portfolio. One of the few late-stage bright spots has been their MET inhibitor tepotinib, which won breakthrough status and now is under priority review. That drug faces a rival at Novartis — capmatinib — that won an accelerated OK at the FDA in May.

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There’s also a BTK inhibitor, evobrutinib, that’s being developed for MS. But that’s a very crowded field, and Sanofi has been bullish about its prospects in the same research niche after buying out Principia.

Moving back into mid-stage development, there’s a major program underway for bintrafusp alfa, a bifunctional fusion protein targeting TGF-β and PD-L1, which Merck KGaA has high hopes for.

That all marks some bright, though limited, prospects for Merck KGaA, highlighting the need to find something new to beef up the pipeline. Bar-Zohar will get a say in that.

AUTHOR
John Carroll

SOURCE

https://endpts.com/novartis-vet-danny-bar-zohar-leaps-back-into-rd-taking-over-the-team-at-merck-kgaa-as-luciano-rossetti-steps-out/

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Double Mutant PI3KA Found to Lead to Higher Oncogenic Signaling in Cancer Cells

Curator: Stephen J. Williams, PhD

PIK3CA (Phosphatidylinsitol 4,5-bisphosphate (PIP2) 3-kinase catalytic subunit α) is one of the most frequently mutated oncogenes in various tumor types ([1] and http://www.sanger.ac.uk/genetics/CGP/cosmic). Oncogenic mutations leading to the overactivation of PIK3CA, especially in context in of inactivating PTEN mutations, result in overtly high signaling activity and associated with the malignant phenotype.

In a Perspective article (Double trouble for cancer gene: Double mutations in an oncogene enhance tumor growth) in the journal Science[2], Dr. Alex Toker discusses the recent results of Vasan et al. in the same issue of Science[3] on the finding that double mutations in the same allele of PIK3CA are more frequent in cancer genomes than previously identified and these double mutations lead to increased PI3K pathway activation, increased tumor growth, and increased sensitivity to PI3K inhibitors in human breast cancer.

 

 

From Dr. Melvin Crasto blog NewDrugApprovals.org

Alpelisib: PIK3CA inhibitor:

Alpelisib: New PIK3CA inhibitor approved for HER2 negative metastatic breast cancer

 

FDA approves first PI3K inhibitor for breast cancer

syn https://newdrugapprovals.org/2018/06/25/alpelisib-byl-719/

Today, the U.S. Food and Drug Administration approved Piqray (alpelisib) tablets, to be used in combination with the FDA-approved endocrine therapy fulvestrant, to treat postmenopausal women, and men, with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative, PIK3CA-mutated, advanced or metastatic breast cancer (as detected by an FDA-approved test) following progression on or after an endocrine-based regimen.

The FDA also approved the companion diagnostic test, therascreen PIK3CA RGQ PCR Kit, to detect the PIK3CA mutation in a tissue and/or a liquid biopsy. Patients who are negative by

May 24, 2019

Today, the U.S. Food and Drug Administration approved Piqray (alpelisib) tablets, to be used in combination with the FDA-approved endocrine therapy fulvestrant, to treat postmenopausal women, and men, with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative, PIK3CA-mutated, advanced or metastatic breast cancer (as detected by an FDA-approved test) following progression on or after an endocrine-based regimen.

The FDA also approved the companion diagnostic test, therascreen PIK3CA RGQ PCR Kit, to detect the PIK3CA mutation in a tissue and/or a liquid biopsy. Patients who are negative by the therascreen test using the liquid biopsy should undergo tumor biopsy for PIK3CA mutation testing.

“Piqray is the first PI3K inhibitor to demonstrate a clinically meaningful benefit in treating patients with this type of breast cancer. The ability to target treatment to a patient’s specific genetic mutation or biomarker is becoming increasingly common in cancer treatment, and companion diagnostic tests assist oncologists in selecting patients who may benefit from these targeted treatments,” said Richard Pazdur, M.D., director of the FDA’s Oncology Center of Excellence and acting director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research. “For this approval, we employed some of our newer regulatory tools to streamline reviews without compromising the quality of our assessment. This drug is the first novel drug approved under the Real-Time Oncology Review pilot program. We also used the updated Assessment Aid, a multidisciplinary review template that helps focus our written review on critical thinking and consistency and reduces time spent on administrative tasks.”

Metastatic breast cancer is breast cancer that has spread beyond the breast to other organs in the body (most often the bones, lungs, liver or brain). When breast cancer is hormone-receptor positive, patients may be treated with anti-hormonal treatment (also called endocrine therapy), alone or in combination with other medicines, or chemotherapy.

The efficacy of Piqray was studied in the SOLAR-1 trial, a randomized trial of 572 postmenopausal women and men with HR-positive, HER2-negative, advanced or metastatic breast cancer whose cancer had progressed while on or after receiving an aromatase inhibitor. Results from the trial showed the addition of Piqray to fulvestrant significantly prolonged progression- free survival (median of 11 months vs. 5.7 months) in patients whose tumors had a PIK3CA mutation.

Common side effects of Piqray are high blood sugar levels, increase in creatinine, diarrhea, rash, decrease in lymphocyte count in the blood, elevated liver enzymes, nausea, fatigue, low red blood cell count, increase in lipase (enzymes released by the pancreas), decreased appetite, stomatitis, vomiting, weight loss, low calcium levels, aPTT prolonged (blood clotting taking longer to occur than it should), and hair loss.

Health care professionals are advised to monitor patients taking Piqray for severe hypersensitivity reactions (intolerance). Patients are warned of potentially severe skin reactions (rashes that may result in peeling and blistering of skin or mucous membranes like the lips and gums). Health care professionals are advised not to initiate treatment in patients with a history of severe skin reactions such as Stevens-Johnson Syndrome, erythema multiforme, or toxic epidermal necrolysis. Patients on Piqray have reported severe hyperglycemia (high blood sugar), and the safety of Piqray in patients with Type 1 or uncontrolled Type 2 diabetes has not been established. Before initiating treatment with Piqray, health care professionals are advised to check fasting glucose and HbA1c, and to optimize glycemic control. Patients should be monitored for pneumonitis/interstitial lung disease (inflammation of lung tissue) and diarrhea during treatment. Piqray must be dispensed with a patient Medication Guide that describes important information about the drug’s uses and risks.

Piqray is the first new drug application (NDA) for a new molecular entity approved under the Real-Time Oncology Review (RTOR) pilot program, which permits the FDA to begin analyzing key efficacy and safety datasets prior to the official submission of an application, allowing the review team to begin their review and communicate with the applicant earlier. Piqray also used the updated Assessment Aid (AAid), a multidisciplinary review template intended to focus the FDA’s written review on critical thinking and consistency and reduce time spent on administrative tasks. With these two pilot programs, today’s approval of Piqray comes approximately three months ahead of the Prescription Drug User Fee Act (PDUFA) VI deadline of August 18, 2019.

The FDA granted this application Priority Review designation. The FDA granted approval of Piqray to Novartis. The FDA granted approval of the therascreen PIK3CA RGQ PCR Kit to QIAGEN Manchester, Ltd.

https://www.fda.gov/news-events/press-announcements/fda-approves-first-pi3k-inhibitor-breast-cancer?utm_campaign=052419_PR_FDA%20approves%20first%20PI3K%20inhibitor%20for%20breast%20cancer&utm_medium=email&utm_source=Eloqua

 

Alpelisib

(2S)-1-N-[4-methyl-5-[2-(1,1,1-trifluoro-2-methylpropan-2-yl)pyridin-4-yl]-1,3-thiazol-2-yl]pyrrolidine-1,2-dicarboxamide

PDT PAT WO 2010/029082

CHEMICAL NAMES: Alpelisib; CAS 1217486-61-7; BYL-719; BYL719; UNII-08W5N2C97Q; BYL 719
MOLECULAR FORMULA: C19H22F3N5O2S
MOLECULAR WEIGHT: 441.473 g/mol
  1. alpelisib
  2. 1217486-61-7
  3. BYL-719
  4. BYL719
  5. UNII-08W5N2C97Q
  6. BYL 719
  7. Alpelisib (BYL719)
  8. (S)-N1-(4-Methyl-5-(2-(1,1,1-trifluoro-2-methylpropan-2-yl)pyridin-4-yl)thiazol-2-yl)pyrrolidine-1,2-dicarboxamide
  9. NVP-BYL719

Alpelisib is an orally bioavailable phosphatidylinositol 3-kinase (PI3K) inhibitor with potential antineoplastic activity. Alpelisib specifically inhibits PI3K in the PI3K/AKT kinase (or protein kinase B) signaling pathway, thereby inhibiting the activation of the PI3K signaling pathway. This may result in inhibition of tumor cell growth and survival in susceptible tumor cell populations. Activation of the PI3K signaling pathway is frequently associated with tumorigenesis. Dysregulated PI3K signaling may contribute to tumor resistance to a variety of antineoplastic agents.

Alpelisib has been used in trials studying the treatment and basic science of Neoplasms, Solid Tumors, BREAST CANCER, 3rd Line GIST, and Rectal Cancer, among others.

 

SYN 2

POLYMORPHS

https://patents.google.com/patent/WO2012175522A1/en

(S)-pyrrolidine-l,2-dicarboxylic acid 2-amide l-(4-methyl-5-[2-(2,2,2-trifluoro-l,l- dimethyl-ethyl)-pyridin-4-yl]-thiazol-2-yl)-amidei hereafter referred to as compound I,

is an alpha-selective phosphatidylinositol 3 -kinase (PI3K) inhibitor. Compound I was originally described in WO 2010/029082, wherein the synthesis of its free base form was described. There is a need for additional solid forms of compound I, for use in drug substance and drug product development. It has been found that new solid forms of compound I can be prepared as one or more polymorph forms, including solvate forms. These polymorph forms exhibit new physical properties that may be exploited in order to obtain new pharmacological properties, and that may be utilized in drug substance and drug product development. Summary of the Invention

In one aspect, provided herein is a crystalline form of the compound of formula I, or a solvate of the crystalline form of the compound of formula I, or a salt of the crystalline form of the compound of formula I, or a solvate of a salt of the crystalline form of the compound of formula I. In one embodiment, the crystalline form of the compound of formula I has the polymorph form SA, SB, Sc, or SD.

In another aspect, provided herein is a pharmaceutical composition comprising a crystalline compound of formula I. In one embodiment of the pharmaceutical composition, the crystalline compound of formula I has the polymorph form SA, SB,Sc, or So.

In another aspect, provided herein is a method for the treatment of disorders mediated by PI3K, comprising administering to a patient in need of such treatment an effective amount of a crystalline compound of formula I, particularly SA, SB, SC,or SD .

In yet another aspect, provided herein is the use of a crystalline compound of formula I, particularly SA, SB, SC, or SD, for the preparation of a medicament for the treatment of disorders mediated by PI3K.

 

Source: https://newdrugapprovals.org/?s=alpelisib&submit=

 

Pharmacology and Toxicology from drugbank.ca

Indication

Alpelisib is indicated in combination with fulvestrant to treat postmenopausal women, and men, with advanced or metastatic breast cancer.Label This cancer must be hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative, and PIK3CA­ mutated.Label The cancer must be detected by an FDA-approved test following progression on or after an endocrine-based regimen.Label

Associated Conditions

Contraindications & Blackbox Warnings

Learn about our commercial Contraindications & Blackbox Warnings data.

LEARN MORE

 

Pharmacodynamics

Alpelisib does not prolong the QTcF interval.Label Patients taking alpelisib experience a dose dependent benefit from treatment with a 51% advantage of a 200mg daily dose over a 100mg dose and a 22% advantage of 300mg once daily over 150mg twice daily.6 This suggests patients requiring a lower dose may benefit from twice daily dosing.6

Mechanism of action

Phosphatidylinositol-3-kinase-α (PI3Kα) is responsible for cell proliferation in response to growth factor-tyrosine kinase pathway activation.3 In some cancers PI3Kα’s p110α catalytic subunit is mutated making it hyperactive.3 Alpelisib inhibits (PI3K), with the highest specificity for PI3Kα.Label

TARGET ACTIONS ORGANISM
APhosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform inhibitor Humans

Absorption

Alpelisib reached a peak concentration in plasma of 1320±912ng/mL after 2 hours.4 Alpelisib has an AUClast of 11,100±3760h ng/mL and an AUCINF of 11,100±3770h ng/mL.4 A large, high fat meal increases the AUC by 73% and Cmax by 84% while a small, low fat meal increases the AUC by 77% and Cmax by 145%.Label

Volume of distribution

The apparent volume of distribution at steady state is 114L.Label

Protein binding

Alpelisib is 89% protein bound.Label

Metabolism

Alpelisib is metabolized by hydrolysis reactions to form the primary metabolite.Label It is also metabolized by CYP3A4.Label The full metabolism of Alpelisib has yet to be determined but a series of reactions have been proposed.4,5 The main metabolic reaction is the substitution of an amine group on alpelisib for a hydroxyl group to form a metabolite known as M44,5 or BZG791.Label Alpelisib can also be glucuronidated to form the M1 and M12 metabolites.4,5

Hover over products below to view reaction partners

Route of elimination

36% of an oral dose is eliminated as unchanged drug in the feces and 32% as the primary metabolite BZG791 in the feces.Label 2% of an oral dose is eliminated in the urine as unchanged drug and 7.1% as the primary metabolite BZG791.Label In total 81% of an oral dose is eliminated in the feces and 14% is eliminated in the urine.Label

Half-life

The mean half life of alprelisib is 8 to 9 hours.Label

Clearance

The mean apparent oral clearance was 39.0L/h.4 The predicted clearance is 9.2L/hr under fed conditions.Label

Adverse Effects

Learn about our commercial Adverse Effects data.

LEARN MORE

 

Toxicity

LD50 and Overdose

Patients experiencing an overdose may present with hyperglycemia, nausea, asthenia, and rash.Label There is no antidote for an overdose of alpelisib so patients should be treated symptomatically.Label Data regarding an LD50 is not readily available.MSDS In clinical trials, patients were given doses of up to 450mg once daily.Label

Pregnancy, Lactation, and Fertility

Following administration in rats and rabbits during organogenesis, adverse effects on the reproductive system, such as embryo-fetal mortality, reduced fetal weights, and increased incidences of fetal malformations, were observed.Label Based on these findings of animals studies and its mechanism of action, it is proposed that alpelisib may cause embryo-fetal toxicity when administered to pregnant patients.Label There is no data available regarding the presence of alpelisib in breast milk so breast feeding mothers are advised not to breastfeed while taking this medication and for 1 week after their last dose.Label Based on animal studies, alpelisib may impair fertility of humans.Label

Carcinogenicity and Mutagenicity

Studies of carcinogenicity have yet to be performed.Label Alpelisib has not been found to be mutagenic in the Ames test.Label It is not aneugenic, clastogenic, or genotoxic in further assays.Label

Affected organisms

Not Available

Pathways

Not Available

Pharmacogenomic Effects/ADRs 

 

Not Available

 

Source: https://www.drugbank.ca/drugs/DB12015

References

  1. Yuan TL, Cantley LC: PI3K pathway alterations in cancer: variations on a theme. Oncogene 2008, 27(41):5497-5510.
  2. Toker A: Double trouble for cancer gene. Science 2019, 366(6466):685-686.
  3. Vasan N, Razavi P, Johnson JL, Shao H, Shah H, Antoine A, Ladewig E, Gorelick A, Lin TY, Toska E et al: Double PIK3CA mutations in cis increase oncogenicity and sensitivity to PI3Kalpha inhibitors. Science 2019, 366(6466):714-723.

 

 

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Tweet Collection by @pharma_BI and @AVIVA1950 and Re-Tweets for e-Proceedings 14th Annual BioPharma & Healthcare Summit, Friday, September 4, 2020, 8 AM EST to 3-30 PM EST – Virtual Edition

Real Time Press Coverage: Aviva Lev-Ari, PhD, RN

 

e-Proceedings 14th Annual BioPharma & Healthcare Summit, Friday, September 4, 2020, 8 AM EST to 3-30 PM EST – Virtual Edition

Real Time Press Coverage: Aviva Lev-Ari, PhD, RN

Founder & Director, LPBI Group

https://pharmaceuticalintelligence.com/2020/07/28/14th-annual-biopharma-healthcare-summit-friday-september-4-2020-8-am-est-to-3-30-pm-est-virtual-edition/

 

Aviva Lev-Ari
@AVIVA1950

#USAIC20 Dr. Hal Barron, Chief Scientific Officer and President R&D, GlaxoSmithKline GWAS not easy to find which gene drives the association  Functional Genomics gene by gene with phenotypes using machine learning significant help

Aviva Lev-Ari
@AVIVA1950

#USAIC20 Dr. Hal Barron, Chief Scientific Officer and President R&D, GSK GWAS not easy to find which gene drives the association  Functional Genomics gene by gene with phenotypes using machine learning significant help

Srihari Gopal
@sgopal2

Enjoyed hearing enthusiasm for Neuroscience R&D by Roy Vagelos at #USAIC20. Wonderful interview by Mathai Mammen

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Aviva Lev-Ari
@AVIVA1950

#USAIC20 Nina Kjellson, General Partner, Canaan Data science is a winner in Healthcare Women – Data Science is an excellent match

Aviva Lev-Ari
@AVIVA1950

#USAIC20 Arpa Garay, President, Global Pharmaceuticals, Commercial Analytics, Merck & Co. Data on Patients and identification who will benefit fro which therapy  cultural bias risk aversion

Aviva Lev-Ari
@AVIVA1950

#USAIC20 Dr. Najat Khan, Chief Operating Officer, Janssen R&D Data Sciences, Johnson & Johnson Data Validation  Deployment of algorithms embed data by type early on in the crisis to understand the disease

Aviva Lev-Ari
@AVIVA1950

#USAIC20 Sastry Chilukuri, President, Acorn AI- Medidata Opportunities in Data Science in Paharma COVID-19 and Data Science

Aviva Lev-Ari
@AVIVA1950

#USAIC20 Dr. Maya Said, Chief Executive Officer, Outcomes4Me Cancer patients taking change of their care Digital Health – consumerization of Health, patient demand to be part of the decision, part the information FDA launched a Program Project Patient Voice

USAIC
@USAIC

We’re taking a quick break at #USAIC20 before our next panel on rare diseases starts at 12:20pm EDT. USAIC would like to thank our Sponsors and Partners for supporting this year’s digital event.

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Aviva Lev-Ari
@AVIVA1950

#USAIC20 Dr. Roy Vagelos, Chairman of the Board, Regeneron HIV-AIDS: reverse transcriptase converted a lethal disease to a chronic disease, tried hard to make vaccine – the science was not there

Aviva Lev-Ari
@AVIVA1950

#USAIC20 Dr. Roy Vagelos, Chairman of the Board, Regeneron Pharmaceuticals Congratulates Big Pharma for taking the challenge on COVID-19 Vaccine, Antibody and anti-viral Government funding Merck was independent from Government – to be able to set the price

1

Dr Kapil Khambholja
@kapilmk

Christopher Viehbacher, Gurnet Point Capital touches very sensitive topic at #USAIC20 He claims that we are never going to have real innovation out of big pharma! Well this isn’t new but not entirely true either… any more thoughts?
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Aviva Lev-Ari
@AVIVA1950

#USAIC20 Daphne Zohar, Founder & CEO, PureTech Health Disease focus, best science is the decision factors

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Aviva Lev-Ari
@AVIVA1950

#USAIC20 Christopher Viehbacher, Managing Partner, Gurnet Point Capital Dream of every Biotech – get Big Pharma coming to acquire and pay a lot Morph and adapt

anju ghangurde
@scripanjug

Biogen’s chair Papadopoulos big co mergers is an attempt to solve problems; typically driven by patent expirations.. #usaic20

2

anju ghangurde
@scripanjug

Chris Viehbacher/Gurnet Point Capital on US election: industry will work with whoever wins; we’ll have to ‘morph & adapt’ #usaic20

1

Dr Kapil Khambholja
@kapilmk

of

talks about various philosophies and key reasons why certain projects/molecules are killed early. My counter questions- What are chances of losing hope little early? Do small #biopharma publish negative results to aid to the knowledge pool? #USAIC20

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Aviva Lev-Ari
@AVIVA1950

#USAIC20 Dr. Laurie Glimcher, President & CEO, Dana-Farber Cancer Institute DNA repair and epignetics are the future of medicine

Aviva Lev-Ari
@AVIVA1950

#USAIC20 Dr. Laurie Glimcher, President & CEO, Dana-Farber Cancer Institute COlonorectal cancer is increasing immuno therapy 5 drugs marketed 30% cancer patients are treated early detection key vs metastatic 10% of cancer are inherited treatment early

Aviva Lev-Ari
@AVIVA1950

#USAIC20 Rehan Verjee, President, EMD Serono Charities funding cancer research – were impacted and resources will come later and in decreased amount New opportunities support access to Medicine improve investment across the board

Aviva Lev-Ari
@AVIVA1950

#USAIC20 Dr. Philip Larsen, Global Head of Research, Bayer AG Repurposing drugs as antiviral from drug screening innovating methods Cytokine storm in OCVID-19 – kinase inhibitors may be antiviral data of tested positive allows research of pathway in new ways

Aviva Lev-Ari
@AVIVA1950

#USAIC20 Dr. Laurie Glimcher, President & CEO, Dana-Farber 3,000 Telemedicine session in the first week of the Pandemic vs 300 before – patient come back visits patient happy with Telemedicine team virtually need be reimbursed same rate working remotely

Aviva Lev-Ari
@AVIVA1950

#USAIC20 Dr. Raju Kucherlapati, Professor of Genetics, Harvard Medical School New normal as a result of the pandemic role of personalized medicine

Aviva Lev-Ari
@AVIVA1950

#USAIC20 Rehan Verjee, President, EMD Serono entire volume of clinical trials at Roche went down same at EMD delay of 6 month, some were to be initiated but was put on hold Charities funding cancer research were impacted and resources will come later smaller

Aviva Lev-Ari
@AVIVA1950

#USAIC20 Dr. Laurie Glimcher, President & CEO, Dana-Farber Cancer Institute Dana Farber saw impact of COVID-19 on immunosuppressed patients coming in for Cancer Tx – switch from IV Tx to Oral 96% decrease in screenings due to Pandemic – increase with Cancer

Aviva Lev-Ari
@AVIVA1950

#USAIC20 Kenneth Frazier, Chairman of the Board and Chief Executive Officer, Merck & Co. Pharma’s obligation for next generations requires investment in R&D vs Politicians running for 4 years Patients must come first vs shareholders vs R&D investment in 2011

Aviva Lev-Ari
@AVIVA1950

#USAIC20 Kenneth Frazier, Chairman of the Board and Chief Executive Officer, Merck & Co. Antibiotic research at Merck – no market incentives on pricing for Merck to invest in antibiotics people will die from bacterial resistance next pandemic be bacterial

Aviva Lev-Ari
@AVIVA1950

#USAIC20 Kenneth Frazier, Chairman of the Board and Chief Executive Officer, Merck & Co. Strategies of Merck = “Medicine is for the People not for Profit” – Ketruda in India is not reembureable in India and million are in need it Partnership are encouraged

Dr Kapil Khambholja
@kapilmk

Chairman Stelios Papadopoulos asks #KennethFrazier if wealthy nations will try to secure large proportion of #COVID19 drugs/vaccines. #KennethFrazie rightly mentions: pharma industry’s responsibility to balance the access to diff countries during pandemic. #USAIC20

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Dr Kapil Khambholja
@kapilmk

Almost 60% participants at #USAIC20 feel that MNCs are more likely to run their #clinicalTrials in #INDIA seeing changing environment here, reveals the poll. Exciting time ahead for scientific fraternity as this can substantially increase the speed of #DrugDevelopment globally

Clapping hands sign

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Aviva Lev-Ari
@AVIVA1950

#USAIC20 Dr. Barry Bloom, Professor & former Dean, Harvard School of Public Health Vaccine in clinical trials, public need to return for 2nd shot, hesitancy Who will get the Vaccine first in the US  most vulnerable of those causing transmission Pharma’s risk

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Aviva Lev-Ari
@AVIVA1950

#USAIC20 Dr. Barry Bloom, Professor & former Dean, Harvard School of Public Health Testing – PCR expensive does not enable quick testing is expensive result come transmission occurred Antibody testing CRISPR test based Vaccine in clinical trials

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Aviva Lev-Ari
@AVIVA1950

#USAIC20 Dr Andrew Plump, President of R&D, Takeda Pharmaceuticals COllaboration effort around the Globe in the Pandemic therapy solutions including Vaccines

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14th Annual BioPharma & Healthcare Summit, Friday, September 4, 2020, 8 AM EST to 3-30 PM EST – Virtual Edition

Real Time Press Coverage: Aviva Lev-Ari, PhD, RN

Founder & Director, LPBI Group

 

Tweet Collection by @pharma_BI and @AVIVA1950 and Re-Tweets for e-Proceedings 14th Annual BioPharma & Healthcare Summit, Friday, September 4, 2020, 8 AM EST to 3-30 PM EST – Virtual Edition

Real Time Press Coverage: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2020/09/04/tweet-collection-by-pharma_bi-and-aviva1950-and-re-tweets-for-e-proceedings-14th-annual-biopharma-healthcare-summit-friday-september-4-2020-8-am-est-to-3-30-pm-est-virtual-editio/

 

 

 

http://www.usaindiachamber.org

 

 2021 summit- June 22. Marriott Cambridge, Massachusetts, USA

 

LPBI’s 2020 VISION

@pharma_BI

@AVIVA1950

#USAIC20

 

 

USAIC has created an ecosystem committed to driving a global dialogue on BioPharma & Healthcare innovation, attracting a diverse mix of senior industry professionals and catalyzing partnerships, new ideas, networks and regulatory reform. This unique platform creates mutually beneficial opportunities and relationships for the global Life Sciences & Healthcare industry.

14th Annual BioPharma & Healthcare Summit, Friday, September 4, 2020, 8 AM EST to 3-30 PM EST – Virtual Edition

 

Speakers


Kenneth Frazier
Chairman of the Board & CEO
Merck & Co.

Dr. Andrew Plump
President of R&D
Takeda Pharmaceuticals

Dr. Laurie Glimcher
President & CEO
Dana-Farber Cancer Institute

Dr. Roy Vagelos
Chairman of the Board
Regeneron

Dr. Stelios Papadopoulos
Chairman of the Board
Biogen

Dr. Mathai Mammen
Global Head of Janssen R&D
Johnson & Johnson

Christopher Viehbacher
Managing Partner
Gurnet Point Capital

Hari Bhartia
Founder & Co-Chairman
Jubilant Bhartia Group

Dr. Hal Barron
President, R&D and CSO
GlaxoSmithKline

Prof. K. Vijay Raghavan
Principal Scientific Advisor
Government of India

Sanat Chattopadhyay
President- Merck Manufacturing Division
Merck & Co.

Dr. George Yancopoulos
Co-Founder, President & CSO
Regeneron

Kiran Mazumdar Shaw
Executive Chairperson
Biocon

Dr. Elias Zerhouni
Professor Emeritus
Johns Hopkins University

Dr. David Reese
Executive Vice President- R&D
Amgen

Dr. Alfred Sandrock
Executive Vice President, R&D
Biogen

Dr. Naresh Trehan
Chairman
Medanta – the Medicity

Dr. Najat Khan
Chief Operating Officer, Data Sciences
Janssen- Johnson & Johnson

Dr. Richard Hatchett
Chief Executive Officer
CEPI

Amitabh Kant
Chief Executive Officer
NITI Aayog

Dr. Martin Mackay
Co-Founder
Rallybio

Dr. Daniel Curran
Head of the Rare Diseases TA
Takeda Pharmaceuticals

Daphne Zohar
Founder & CEO
PureTech Health

Dr. David Meeker
Chairman & CEO
Rhythm Pharmaceuticals

Dr. John Orloff
EVP and Head of R&D
Alexion

Dr. Mandeep Bhandari
Joint Secretary
Ministry of Health, India

Dr. Barry Bloom
Professor & former Dean
Harvard School of Public Health

Dr. Anne Heatherington
Head of Data Sciences Institute
Takeda Pharmaceuticals

Dr. Philip Larsen
Global Head of Research
Bayer AG

Dr. Timothy Yu
Assistant Professor in Pediatrics
Harvard Medical School

Rehan Verjee
President
EMD Serono

Sastry Chilukuri
Executive Vice President
Medidata

Arpa Garay
President, Commercial Analytics
Merck & Co.

Dr. William Chin
Professor of Medicine, Emeritus
Harvard Medical School

Dr. V G Somani
Drugs Controller General of India
Government of India

Dr. Rajeev Venkayya
President-Global Vaccines
Takeda

Dr. Steve Uden
Co-Founder
Rallybio

Muna Bhanji
SVP, Global Market Access
Merck & Co.

Dr. Maya Said
Chief Executive Officer
Outcomes4Me

Dr. Raju Kucherlapati
Professor of Genetics
Harvard Medical School

Dr. Tony Ho
Head of R&D
CRISPR Therapeutics

Dr. Sanjeev Sinha
Professor of Medicine
All India Institute of Medical Sciences

Nina Kjellson
General Partner
Canaan

Dr. Michael Rosenblatt
Chief Medical Officer
Flagship Pioneering

Dr. Shiv Kumar Sarin
Director
Institute of Liver & Biliary Sciences

Matt Wilsey
Co-Founder & Chairman
Grace Science Foundation

Dr. Samuel Waksal
Founder
Meira GTx

Dr. Alise Reicin
Former President, Global Clinical Dev.
Celgene

Dr. Toni Choueiri
Director
Lank Center for Genitourinary Oncology
Dana-Farber Cancer Institute

Dr. Dhaval Patel
EVP & Chief Scientific Officer
UCB

Dr. Nirmal Kumar Ganguly
Former Director General
Indian Council of Medical Research

Dr. Peter Mueller
President
The Muller Health Foundation

Dr. Timothy Clackson
President & CTO
Xilio Therapeutics
 

 

14th Annual BioPharma & Healthcare Summit, Friday, September 4, 2020,

8 AM EST to 3-30 PM EST – Virtual Edition

 

Chair and Master of Ceremonies (Emcee)– Dr. Andrew Plump, President of R&D, Takeda Pharmaceuticals

Timings are Eastern Standard Time (EST)

Time Topic
8 AM – 8-10 AM Welcome addressKarun Rishi, President, USAIC

  • COVID-19 Pandemic is a Global crisis
  • India can play a special role in R&D and in Manufacturing including Vaccine development

Opening commentsDr Andrew Plump, President of R&D, Takeda Pharmaceuticals

  • Global Summit around the World – JP Morgan of the East as we were called – it is Now a Global Conference vs East Coast
  • Record number of Drugs approved as New Drugs with special quality
  • explosion of modality of therapies to include Gene Therapy
  • Billion underserved vs N-of-One drug
  • India’s President Modi allow healthcare access to 1/2Billion
  • collaboration across the World COVID Alliance in vaccine development
  • Global effort, China recovery is remarkable
  • India battle the infection and it is growing – Public Health
  • Remarkable Speakers
8-10 AM – 8-50 AM Panel Discussion- COVID-19: Where are we now? Where are we going?

Panelists:
Dr. Barry Bloom, Professor & former Dean, Harvard School of Public Health

  • Testing – PCR expensive does not enable quick testing is expensive result come transmission occurred
  • Antibody testing
  • CRISPR test based
  • Vaccine in clinical trials, public need to return for 2nd shot, hesitancy
  • Who will get the Vaccine first? in the US  most vulnerable of those causing transmission
  • Pharma takes risk when efficacious level is unknown
    Dr. George Yancopoulos, Co-Founder, President & CSO, Regeneron
  • Repurpose – be careful
  • Ebola vaccine development approach is been REUSED for COVID-19
  • Existential threat by Disease – preparedness is ridiculous as size of investment – far where we need to be
  • Untreatable disease burden COVID-19 cost of healthcare calls massive increases as a society and Private sector Moderna invested in new technology from Academe to the Industry
  • Universal HealthCare will cripple the the healthcare systems
    Kiran Mazumdar-Shaw, Executive Chairperson, Biocon
  • Safety in proof of concept
  • Children focus for emergency use
  • validation of repurpose drugs
  • oral vaccine involve sequential processing, approval and TRUST,
  • concerns about risks
  • accelerate the process is the opportunity
    Dr. Rajeev Venkayya, President of the Global Vaccine Business Unit, Takeda
  • Public confidence in COVID-19 Vaccine
  • The Group with concerns at present is larger than 15 years ago due to the accelerate process od the development process
  • political influences on CDC emergency authorization given prior to election
  • hesitancy – influence of social media, conspiracies
  • Transparency by Pharma and by Regulatory Agencies
  • Independent reviews
    Dr. Richard Hatchett, CEO, Coalition for Epidemic Preparedness Innovations (CEPI)
  • 78 countries ready to participate, Healthcare workers priority to be ready end of next year

 

Moderator:
Dr. William Chin, Professor of Medicine, Emeritus, Harvard Medical School

8-50 AM – 8-55 AM Break + Polling
8-55 AM – 9-10 AM India Regulatory update

Dr. Mandeep Bhandari, Joint Secretary, Ministry of Health & Family Welfare, India

  • COVID related – support for Clinical Trials support to the Industry, innovators, processes and infrastructure is in place

Dr. V G Somani, Drug Controller General of India, Central Drug Control Organization

  • partnership, time line, transparency
  • interaction online with regulators
  • 30 days approval pre and post approval – progress achieved
  • Online presubmission very useful to both sides
  • Ecosystems on early development: Gene therapy

Moderator:
Muna Bhanji, Senior Vice President,  Merck & Co.

  • India’s preparedness
9-10 AM – 9-15 AM Break + Polling
9-15 AM – 9-55 AM Fireside Chat

Kenneth Frazier, Chairman of the Board and Chief Executive Officer, Merck & Co.

Strategies of Merck = “Medicine is for the People not for Profit”

  • AntiViral – nucleocide – orally bioavailable
  • Vaccine in early development – BSV Vaccine used in EBOLA – attenuated virus vector platform experience – 1 single doze, deployed Globally
  • Vaccine modified Measles Vaccine, novel platform – out patient and Hospital
  • Antibiotic research at Merck – no market incentives on pricing for Merck to invest in antibiotics
  • people will die from bacterial resistance infection and next pandemic will be bacterial not viral

Moderator:
Dr. Stelios Papadopoulos, Chairman of the Board, Biogen

  • Most important comments on urgency in investment in drug development by multiple constituencies made by
  • Dr. George Yancopoulos, Co-Founder, President & CSO, Regeneron
  • Access to therapy
9-55 AM – 10 AM Break + Polling
10 AM – 10-40 AM India Innovation Landscape

Panelists:
Amitabh Kant, Chief Executive Officer, National Institution for Transforming India (NITI)

  • Innovation in drug discovery collaboration for clinical trial infrastructure
  • BioEconomy BioSimilar the largest number approved anywhere
  • Incentives for size and scale
  • Ingredients manufacturing to become India’s priority
  • Investment in R&D and Human Capital in the BioEconomy

Hari Bhartia, Founder & Co-Chairman, Jubilant Bhartia Group

  • US history of innovations cluster and infrastructure: Academe, VC, small medium Biopharma, Government involvement
  • India: Contract research – 20 years history, lagging the ability to take risk
  • Changing, pricing of drug increased, innovating drug for local consumption, and it can be taken to US for a better price
  • Cancer immunology in India under development
  • India was Leading Chemistry Research – China’s government invested and took the market
  • Indian companies bigger in size – free on requirement imposed on China
  • India will be a great supplier to US Market to build high capacity raw materials

Dr. K. Vijay Raghavan, Principal Scientific Advisor, Government of India

Resources are necessary 30% from Industry vs Government and Academe with great students and labs

Indian context – Personalized Medicine – Telemedicine and IT infrastructure allowing innovation in a 1Billion Population- sheer volume of quality professional

Dr. Naresh Trehan, Chairman, Medanta – the Medicity

  • Ecosystem ready for Government to promote innovations to conduct clinical trial with global acceptance standard
  • diverse gene pool in population to innovate for new molecule to market
  • Vaccine under development on Phase 1,2,3 – regulatory mechanism is in place
  • genetic drugs, BioSimilar dominance in the market – biotech can do clinical trials in India vs abroad

Moderator:
Sanat Chattopadhyay, President, Merck Manufacturing Division; Merck & Co.

  • Largest producer of generic drugs
  • antiretroviral drug produced by Indian Pharma
  • Biotech innovations growing middle class – how innovation , infrastructure and shift to research
  • Diversify and become self reliance
10-40 AM – 10-45 AM Break + Polling
10-45 AM – 11-25 AM Panel Discussion- Oncology: Changing landscape- COVID learnings and the promise of new technologies

Panelists:
Dr. Alise Reicin, Former President, Global Clinical Development, Celgene

  • Clinical trial were impacted by association of patients to trials
  • anti bacterial resistance requires investment – needs will be greater for antibiotics in the future
  • Cancer mutation next therapy biomarkers for mutations to be developed

Dr. Laurie Glimcher, President & CEO, Dana-Farber Cancer Institute

  • Dana Farber saw impact of COVID-19 on immunosuppressant population of patients coming in for Cancer Tx – switch from IV Tx to Oral
  • 96% decrease in screenings due to Pandemic – increase with Cancer diagnosis in coming years
  • No clinical Trials in Cancer were suspended – all continued
  • Telemedicine and working at home very efficient
  • Genomics of COVID-19 studies at Dana Farber same pathway identifies
  • safety and efficacy must be achieved – not to approve drugs without phase I & Phase II endpoints

Dr. Philip Larsen, Global Head of Research, Bayer AG

  • Repurposing drugs as antiviral from drug screening innovating methods
  • Cytokine storm in OCVID-19 – kinase inhibitors may be antiviral  – dat of tested positive allows research of pathway in new ways
  • Regulatory agencies in US and Europe for types of drugs vs single patient drugs

Rehan Verjee, President, EMD Serono

  • entire volume of clinical trials at Roche went down same at EMD
  • delay of 6 month, some were to be initiated but was put on hold
  • Charities funding cancer research – were impacted and resources will come later and in decreased amount
  • New opportunities support access to Medicine
  • improve investment across the board
  • Antibody cytotoxic with precision

Dr. Tony Ho, Head of Research and Development, CRISPR Therapeutics

  • challenges overcome by testing at home

Moderator:
Dr. Raju Kucherlapati, Professor of Genetics, Harvard Medical School

  • New normal as a result of the pandemic role of personalized medicine
  • Cancer cure – what are the prospects
11-25 AM – 11-30 AM Break + Polling
11-30 AM – 12-10 PM Panel Discussion- Industry & Investment Outlook

Panelists:
Christopher Viehbacher, Managing Partner, Gurnet Point Capital

  • IPOs can have advantages in Pandemics – Travel curtails all deals done virtually in greater efficiency
  • Drug pricing is a target by White house
  • Dream of every Biotech – get Big Pharma coming to acquire and pay a lot
  • Morph and adapt

Daphne Zohar, Founder & CEO, PureTech Health

  • kill project early financial incentive not in line in the industry
  • incentive to move resources among project and kill early project experiments to find which project to kill
  • Innovations – pattern recognition, fast followers academic translation
  • Disease focus, best science is the decision factors

Dr. Elias Zerhouni, Professor Emeritus, Johns Hopkins University

  • Digital Health
  • CVS opens clinics
  • R&D – Capital is low
  • Network of global innovation hubs vc investor channel like in the past
  • Value of company driven by hits blockbusters

 

Dr. Stelios Papadopoulos, Chairman, Biogen

  • Worst pandemic in our lifetime
  • stock market if hot – in balance in supply and demand, interest rates low, excess supply of equities in entertainment, Travel, hospitality
  • Healthcare was defensive therapeutics needed – opportunity to innovate in HC – shift money from entertainment, Travel hospitality to HC
  • Recovery will shift money away from Healthcare
  • IP Protection and patent expiration – biotech are cases not trends

Moderator:

Dr. Andrew Plump,

President of Research & Development, Takeda Pharmaceuticals

Moderator Presenter: Dr. Michael Rosenblatt, CEO

12-10 PM – 12-20 PM Break + Polling
12-20 PM – 1 PM Panel Discussion- Rare Diseases: No longer forgotten; but more to be achieved

ROI is not there, regulatory requirements reduced, Registry

Panelists:
Dr. Alfred Sandrock, Executive Vice President, Research & Development, Biogen

  • Multiple Sclerosis therapy
  • cost effectiveness is not there vs save a life
  • Appeal opportunity is there and regulators are people

Dr. Daniel Curran, Head of the Rare Diseases Therapeutic Area Unit, Takeda

  • Takeda collaborates with Grace Science Foundation

Dr. David Meeker, Chairman & CEO , Rhythm Pharmaceuticals

  • Cystic Fibrosis 

Dr. John Orloff, Head of Research & Development, Alexion

  • ALS
  • Duchenne Muscular Destrophy
  • HUS
  • ASO
  • gene therapy – one time therapy: Valuation for the industry of long term therapy: US (long term non existence) vs Europe and Japan (much appreciated

Matt Wilsey, Co-Founder & Chairman, Grace Science Foundation

  • Ultra-rare (500 Patients) vs Ultra Ultra-rare (50 Patients)
  • 70 patients in the World, Grace disease, Parent drive the search for drug
  • Manufacturing cost comes down
  • Price is dynamic

Moderator:
Dr. Steve Uden, Co-Founder, Rallybio

  • Regulators are people

 

1 PM – 1-05 PM Break + Polling
1-05 PM – 1-50 PM Fireside Chat

Dr. Roy Vagelos, Chairman of the Board, Regeneron Pharmaceuticals

  • Congratulate Big Pharma for taking the challenge on COVID-19
  • Vaccine, Antibody and anti-viral
  • Government funding
  • Merck was independent from Government – to be independent and be able to set the price
  • HIV-AIDS: reverse transcriptase converted a lethal disease to a chronic disease, tried hard to make vaccine – the science was not there
  • Industry role: Competition of drug discovery capacity is been built, global needs, price need be low for global reach
  • Government is a already a player hoping without a control on pricing
  • 300Million people were treated FREE by Merck’s Family Program HepC
  • 9% in China immunize the newborn with HepB 1994 100% babies immunized – no profit to Merck – eradication of HepB in China
  • Neuro degeneration – science supports drug development
  • Role of R&D Scientists in Drug discovery?

Moderator:
Dr. Mathai Mammen, Global Head of Janssen Research & Development, Johnson & Johnson

  • COVID-19 drug development: Response by Big Pharma
  • Industry role in Access to medicines, biologics, antibodies, vaccines
  • Role of R&D Scientists in Drug discovery?
  • PAHTN – use Machine Learning on top of data collected routinely,

 

1-50 PM – 1-55 PM Break + Polling
1-55 PM – 2-35 PM Panel Discussion- Digital & Data Science in Healthcare: Pragmatic Insights from the Real-World

Panelists:
Dr. Anne Heatherington, Head of Data Sciences Institute, Takeda Pharmaceuticals

  • Reliance on Data – AI and Data in Pharma alliance with MIT
  • collaboration of Data for COVID-19
  • Women need education in STEM and in Data Science

Arpa Garay, President, Global Pharmaceuticals, Commercial Analytics, Merck & Co.

  • Data on Patients and identification who will benefit fro which therapy
  •  cultural bias risk aversion
  • Invest early on in STEM

Dr. Maya Said, Chief Executive Officer, Outcomes4Me

  • Cancer patients taking change of their care
  • Digital Health – consumerization of Health, patient demand to be part of the decision, part of the information
  • FDA launched a Program Project Patient Voice

https://www.fda.gov/about-fda/oncology-center-excellence/project-patient-voice

  • Women should not undersell themselves

Dr. Najat Khan, Chief Operating Officer, Janssen R&D Data Sciences, Johnson & Johnson

  • Validation
  • Deployment of algorithms
  • embed data by type early on in the crisis to understand the disease
  • Compare the Big IT-Data and Pharma where are the barriers?
  • STEM and Women in Pharma – the opportunity must be right

Nina Kjellson, General Partner, Canaan

  • Data science is a winner in Healthcare
  • Women – Data Science is an excellent match

Moderator:
Sastry Chilukuri, President, Acorn AI- Medidata

  • Opportunities in Data Science in Pharma
  • COVID-19 and Data Science
  • STEM and Women in Pharma

 

2-35 PM – 2-40 PM Break + Polling
2-40 PM – 3-20 PM Panel Discussion- R&D Strategies and Trends: Innovation – The Big I

Panelists:
Dr. Andrew Plump, President of Research & Development, Takeda Pharmaceuticals

  • Enter for Plasma and for manufacturing vs discovery
  • Change how pharma behaved inefficiently in the past – with COVID-19 new behaviors in the industry
  • End of Century most diseases could be cured

Dr. David Reese, Executive Vice President, Research and Development, Amgen

  • Interaction with regulator was most favorable

Dr. Hal Barron, Chief Scientific Officer and President R&D, GlaxoSmithKline

  • Cytokine storm – few approaches
  • Control molecule GSK owned
  • GWAS not easy to find which gene drives the association
  • Functional Genomics gene by gene with phenotypes using machine learning significant help

Dr. Mathai Mammen, Global Head of Janssen Research & Development, Johnson & Johnson

  • Neuro-modulation: Symptomology Outcomes – no correlation
  • Vaccine platform used in the past for several vaccines: Selection process from several candidates, cell line enter Clinical waiting for data
  • Using same platform with several proteins – great communality in the development
  • Regulator deepen trust relationship which will carry for the future
  • Pulmonologists and cardiologist in the COVIS-19 Patients – remove drugs monitoring on drugs

Moderator:
Duval Patel presented the Moderator

Moderator:

Martin Mackay, Co-Founder, RallyBio

 

3-20 PM – 3-30 PM Closing Remarks

  • Every year it is getting better
  • India – innovate and make drugs for every country and for India
  • Diversity and inclusion
  • Leadership in Pharma Industry in all Panels
  • Massive impact can be made

 

Poll Questions for September 4

Polling Time (EST) Polling Topic
8-50 AM COVID-19 PanelQuestion 1: What do you foresee as the most likely outcome of the race to develop a vaccine?

  • Heightened international tensions due to inequities in distribution
  • Use of the vaccine as an instrument of geopolitics
  • Collaboration between governments to use vaccine to end the pandemic
  • All of the above

Question 2: What minimum criteria would you like to see for approval of COVID19 vaccines, assuming adequate efficacy?

  • Immune response in people over 60 years
  • Durability of response
  • Antibody plus T-cell response
  • Emergency Use Authorization with caveats followed by final approval
9-10 AM India Regulatory UpdateHow will MNCs respond to the recent regulatory changes for BioPharmas in India? They are _____ to run clinical trials there:

  • More likely
  • Less likely
  • Equally likely
9-55 AM Fireside Chat: Ken Frazier

The BioPharma industry this year has publicly committed itself to greater diversity. What specific measures do you expect to see?

  • Increasing diversity in clinical trials
  • Increasing diversity at the C-suite and board level
  • Increasing diversity throughout the company
  • All of the above
  • None of the above
10-40 AM India Innovation LandscapeWhat is the most important step India could take to become a global leader in life sciences innovation?”

  • Implement government policies to incentivize innovative drug development
  • Increase availability of financing for BioPharmas
  • Improve clinical trial infrastructure
  • Increase IP protection
11-25 AM Oncology PanelQuestion 1:

Changes in policy and reimbursement over the next five years will impact innovation in cancer therapeutics

  • Not at all
  • Slightly
  • Moderately
  • Significantly

Question 2: What therapeutic innovation do you think will have the biggest impact on cancer in the next five years?

  • Cell-based immunotherapies
  • Antibody-based immunotherapies
  • Bispecific / multi-specific antibodies
  • Antibody drug conjugates
12-10 PM Industry & Investment Outlook PanelMore and more funding has been going into preclinical companies — do you expect this trend to continue?

  • Yes
  • No

R&D Strategies and Trends Panel

COVID-19 has led to an unprecedented level of collaboration among stakeholders in the biopharma industry. Where do you expect to see the biggest increase in collaborations post-pandemic?

  • Discovery/preclinical research
  • Clinical development
  • Manufacturing
  • Commercialization
1 PM Rare Diseases PanelWhat is the biggest barrier to access to Orphan drugs in low-income countries?

  • Price, Access and Availability
  • Disease recognition and diagnosis
  • Lack of patient education regarding new therapies
  • Ultra-rarity of certain diseases creates barriers for BioPharma companies to pursue therapeutic
1-50 PM Fireside Chat: Roy VagelosQuestion 1:

Will pharma’s reputation continue its positive trend or return to negative base line beyond the pandemic

  • Yes
  • No

Question 2:

COVID-19 has put the spotlight on BioPharma as an essential player in the return to normalcy. What primary action do you think the industry needs to take to maintain a positive reputation beyond the pandemic?

  • Continue developing innovative drug pricing models
  • Increase drug pricing transparency
  • Increase data sharing and transparency
  • Improving availability and access in low income countries
2-35 PM Digital & Data Sciences PanelWhere has COVID-19 had the biggest impact on your adoption and use of digital health technologies?

  • Remote clinical trials and patient monitoring
  • Real-world data collection and analysis
  • Virtual drug launches

 

@@@@

In these unprecedented times due to COVID-19, USAIC is offering Free Registration for its annual summit.

Click for free registration

 

AGENDA & SPEAKERS

Chair and Master of Ceremonies (Emcee)– Dr. Andrew Plump, President of R&D, Takeda Pharmaceuticals
Summit Theme: “From N of One to N of a Billion”

  • Moderated Fireside Chat- Kenneth Frazier, Chairman of the Board and Chief Executive Officer, Merck & Co. and Stelios Papadopoulos, Chairman of the Board, Biogen
  • Moderated Fireside Chat- Roy Vagelos, Chairman of the Board, Regeneron Pharmaceuticals and Mathai Mammen, Global Head of R&D, Janssen Pharmaceutical Companies of Johnson & Johnson
  • Moderated Fireside Chat- K. VijayRaghavan, Principal Scientific Advisor, Government of India and Amitabh Kant, CEO, National Institution for Transforming India (NITI)

Panel Discussions:

  • Covid-19: Where are we now? Where are we going?
  • Oncology: A never ending tunnel?
  • Rare Diseases: Breaking Barriers for a Healthy Brain
  • Digital & Data Sciences: Leveraging data and digital to achieve healthcare solutions
  • Industry & Investment Outlook
  • R&D Strategies and Trends: Innovation – The Big I

Program and speakers subject to change*

14th Annual BioPharma & Healthcare Summit, Friday, September 4, 2020, 8 AM EST to 3-30 PM EST – Virtual Edition

Speakers


Kenneth Frazier
Chairman of the Board & CEO
Merck & Co.

Dr. Andrew Plump
President of R&D
Takeda Pharmaceuticals

Dr. Laurie Glimcher
President & CEO
Dana-Farber Cancer Institute

Dr. Roy Vagelos
Chairman of the Board
Regeneron

Dr. Stelios Papadopoulos
Chairman of the Board
Biogen

Christopher Viehbacher
Managing Partner
Gurnet Point Capital

Dr. Mathai Mammen
Global Head of R&D
Janssen- Johnson & Johnson

Kiran Mazumdar Shaw
Chairperson & Managing Director
Biocon

Dr. Hal Barron
President, R&D and CSO
GlaxoSmithKline

Prof. K. Vijay Raghavan
Principal Scientific Advisor
Government of India

Dr. George Yancopoulos
Co-Founder, President & CSO
Regeneron

Dr. Elias Zerhouni
Professor Emeritus
Johns Hopkins University

Daphne Zohar
Founder & CEO
PureTech Health

Sanat Chattopadhyay
President- Merck Manufacturing Division
Merck & Co.

Dr. David Reese
Executive Vice President- R&D
Amgen

Hari Bhartia
Founder & Co-Chairman
Jubilant Bhartia Group

Dr. Alfred Sandrock
Exe Vice President R&D & CMO
Biogen

Dr. Najat Khan
Chief Operating Officer, Data Sciences
Janssen- Johnson & Johnson

Dr. Richard Hatchett
Chief Executive Officer
CEPI

Amitabh Kant
Chief Executive Officer
NITI Aayog

Dr. Martin Mackay
Co-Founder
Rallybio

Dr. Daniel Curran
Head of the Rare Diseases TA
Takeda Pharmaceuticals

Dr. Alise Reicin
Former President, Global Clinical Dev.
Celgene

Dr. David Meeker
Chairman & CEO
Rhythm Pharmaceuticals

Dr. John Orloff
EVP and Head of R&D
Alexion

Dr. Barry Bloom
Professor & former Dean
Harvard School of Public Health

Dr. Mandeep Bhandari
Joint Secretary
Ministry of Health, India

Arpa Garay
President, Commercial Analytics
Merck & Co.

Dr. Steve Uden
Co-Founder
Rallybio

Dr. Philip Larsen
Global Head of Research
Bayer AG

Sastry Chilukuri
Executive Vice President
Medidata

Dr. William Chin
Professor of Medicine, Emeritus
Harvard Medical School

Dr. Anne Heatherington
Head of Data Sciences Institute
Takeda Pharmaceuticals

Dr. V G Somani
Drugs Controller General of India
Government of India

Dr. Rajeev Venkayya
President-Global Vaccines
Takeda

Dr. Raju Kucherlapati
Professor of Genetics
Harvard Medical School

Matt Wilsey
Co-Founder & Chairman
Grace Science Foundation

Muna Bhanji
SVP, Global Market Access
Merck & Co.

Dr. Maya Said
Chief Executive Officer
Outcomes4Me

Rehan Verjee
President
EMD Serono
Pharmasia News Biospectrum India Online

SOURCE:

https://usaindiachamber.org/speaker.php

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National Public Radio interview with Dr. Anthony Fauci on his optimism on a COVID-19 vaccine by early 2021

Reporter: Stephen J. Williams, PhD

Below I am giving a link to an important interview by NPR’s Judy Woodruff with Dr. Anthony Fauci on his thoughts regarding the recent spikes in cases, the potential for a COVID-19 vaccine by next year, and promising therapeutics in the pipeline.  The interview link is given below however I will summarize a few of the highlights of the interview.

 

Some notes on the interview

Judy Woodruff began her report with some up to date news regarding the recent spike and that Miami Florida has just ordered the additional use of facemasks.  She asked Dr. Anthony Fauci, head of the National Institute of Allergy and Infectious Diseases (NIAD), about if the measures currently in use are enough to bring this spike down.  Dr. Fauci said that we need to reboot our efforts, mainly because people are not doing three things which could have prevented this spike mainly

  1. universal wearing of masks
  2. distancing properly from each other
  3. close the bars and pubs (see Wisconsin bars packed after ruling)

It hasn’t been a uniform personal effort

Dr. Fauci on testing

We have to use the tests we have out there efficiently and effectively And we have to get them out to the right people who can do the proper identification, isolation, and do proper contract tracing and need to test more widely in a surveillance way to get a feel of the extent and penetrance of this community spread.  there needs to be support and money for these testing labs

We have a problem and we need to admit and own it but we need to do the things we know are effective to turn this thing around.

On Vaccines

“May be later this year”

His response to Merck’s CEO Ken Frazer who said officials are giving false hop if they say ‘end of year’ but Dr. Fauci disagrees.  He says a year end goal is not outlandish.

What we have been doing is putting certain things in line with each other in an unprecedented way.

Dr. Fauci went on to say that, in the past yes, it took a long time, even years to develop a vaccine but now they have been able to go from sequence of virus to a vaccine development program in days, which is unheard of.  Sixty two days later we have gone into phase 1 trials. the speed at which this is occurring is so much faster.  He says that generally it would take a couple of years to get a neutralizing antibody but we are already there.  Another candidate will be undergoing phase 3 trials by end of this month (July 2020).

He is “cautiously optimistic” that we will have one or more vaccines to give to patients by end of year because given the amount of cases it will be able to get a handle on safety and efficacy by late fall.

Now he says the game changer is that the government is working with companies to ramp up the production of doses of the candidate vaccines so when we find which one works we will have ample doses on hand.  He is worried about the anti vaccine movement derailing vaccine testing and vaccinations but says if we keep on informing the public we can combat this.

Going back to school

Dr. Fauci is concerned for the safety of the vulnerable in schools, including students and staff.  He wants the US to get down to a reasonable baseline of cases but in the US that baseline after the first wave was still significantly higher than in most countries, where the baseline was more like tens of cases not hundreds of cases.

For more information on COVID-19 Please go to our Coronavirus Portal at

https://pharmaceuticalintelligence.com/coronavirus-portal/

 

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From Cell Press:  New Insights on the D614G Strain of COVID: Will a New Mutated Strain Delay Vaccine Development?

Reporter: Stephen J. Williams, PhD

Two recent articles in Cell Press, both peer reviewed, discuss the emergence and potential dominance of a new mutated strain of COVID-19, in which the spike protein harbors a D614G mutation.

In the first article “Making Sense of Mutation: What D614G means for the COVID-19 pandemic Remains Unclear”[1] , authors Drs. Nathan Grubaugh, William Hanage, and Angela Rasmussen discuss the recent findings by Korber et al. 2020 [2] which describe the potential increases in infectivity and mortality of this new mutant compared to the parent strain of SARS-CoV2.  For completeness sake I will post this article as to not defer from their interpretations of this important paper by Korber and to offer some counter opinion to some articles which have surfaced this morning in the news.

Making sense of mutation: what D614G means for the COVID-19 pandemic remains unclear

 

Nathan D. Grubaugh1 *, William P. Hanage2 *, Angela L. Rasmussen3 * 1Department of Epidemiology of Microbial Diseases, Yale School of Public Health, New Haven, CT 06510, USA 2Center for Communicable Disease Dynamics, Department of Epidemiology, Harvard T. H. Chan School of Public Health, Boston, MA 02115, USA 3Center for Infection and Immunity, Columbia Mailman School of Public Health, New York, NY 10032, USA Correspondence: grubaughlab@gmail.com

 

Abstract: Korber et al. (2020) found that a SARS-CoV-2 variant in the spike protein, D614G, rapidly became dominant around the world. While clinical and in vitro data suggest that D614G changes the virus phenotype, the impact of the mutation on transmission, disease, and vaccine and therapeutic development are largely unknown.

Introduction: Following the emergence of SARS-CoV-2 in China in late 2019, and the rapid expansion of the COVID19 pandemic in 2020, questions about viral evolution have come tumbling after. Did SARS-CoV-2 evolve to become better adapted to humans? More infectious or transmissible? More deadly? Virus mutations can rise in frequency due to natural selection, random genetic drift, or features of recent epidemiology. As these forces can work in tandem, it’s often hard to differentiate when a virus mutation becomes common through fitness or by chance. It is even harder to determine if a single mutation will change the outcome of an infection, or a pandemic. The new study by Korber et al. (2020) sits at the heart of this debate. They present compelling data that an amino acid change in the virus’ spike protein, D614G, emerged early during the pandemic, and viruses containing G614 are now dominant in many places around the world. The crucial questions are whether this is the result of natural selection, and what it means for the COVID-19 pandemic. For viruses like SARS-CoV-2 transmission really is everything – if they don’t get into another host their lineage ends. Korber et al. (2020) hypothesized that the rapid spread of G614 was because it is more infectious than D614. In support of their hypothesis, the authors provided evidence that clinical samples from G614 infections have a higher levels of viral RNA, and produced higher titers in pseudoviruses from in vitro experiments; results that now seem to be corroborated by others [e.g. (Hu et al., 2020; Wagner et al., 2020)]. Still, these data do not prove that G614 is more infectious or transmissible than viruses containing D614. And because of that, many questions remain on the potential impacts, if any, that D614G has on the COVID-19 pandemic.

The authors note that this new G614 variant has become the predominant form over the whole world however in China the predominant form is still the D614 form.  As they state

“over the period that G614 became the global majority variant, the number of introductions from China where D614 was still dominant were declining, while those from Europe climbed. This alone might explain the apparent success of G614.”

Grubaugh et al. feel there is not enough evidence that infection with this new variant will lead to higher mortality.  Both Korber et al. and the Seattle study (Wagner et al) did not find that the higher viral load of this variant led to a difference in hospitalizations so apparently each variant might be equally as morbid.

In addition, Grubaugh et al. believe this variant would not have much affect on vaccine development as, even though the mutation lies within the spike protein, D614G is not in the receptor binding domain of the spike protein.  Korber suggest that there may be changes in glycosylation however these experiments will need to be performed.  In addition, antibodies from either D614 or G614 variant infected patients could cross neutralize.

 

Conclusions: While there has already been much breathless commentary on what this mutation means for the COVID19 pandemic, the global expansion of G614 whether through natural selection or chance means that this variant now is the pandemic. As a result its properties matter. It is clear from the in vitro and clinical data that G614 has a distinct phenotype, but whether this is the result of bonafide adaptation to human ACE2, whether it increases transmissibility, or will have a notable effect, is not clear. The work by Korber et al. (2020) provides an early base for more extensive epidemiological, in vivo experimental, and diverse clinical investigations to fill in the many critical gaps in how D614G impacts the pandemic.

The link to the Korber Cell paper is here: https://www.cell.com/cell/fulltext/S0092-8674(20)30820-5

Tracking changes in SARS-CoV-2 Spike: evidence that D614G increases infectivity of the COVID-19 virus

DOI: https://doi.org/10.1016/j.cell.2020.06.043

Keypoints

  • The consistent increase of G614 at regional levels may indicate a fitness advantage

 

  • G614 is associated with lower RT PCR Ct’s, suggestive of higher viral loads in patients

 

  • The G614 variant grows to higher titers as pseudotyped virions

Summary

A SARS-CoV-2 variant carrying the Spike protein amino acid change D614G has become the most prevalent form in the global pandemic. Dynamic tracking of variant frequencies revealed a recurrent pattern of G614 increase at multiple geographic levels: national, regional and municipal. The shift occurred even in local epidemics where the original D614 form was well established prior to the introduction of the G614 variant. The consistency of this pattern was highly statistically significant, suggesting that the G614 variant may have a fitness advantage. We found that the G614 variant grows to higher titer as pseudotyped virions. In infected individuals G614 is associated with lower RT-PCR cycle thresholds, suggestive of higher upper respiratory tract viral loads, although not with increased disease severity. These findings illuminate changes important for a mechanistic understanding of the virus, and support continuing surveillance of Spike mutations to aid in the development of immunological interventions.

 

References

  1. Grubaugh, N.D., Hanage, W.P., Rasmussen, A.L., Making sense of mutation: what D614G means for the COVID-19 pandemic remains unclear, Cell (2020), doi: https:// doi.org/10.1016/j.cell.2020.06.040.
  2. Korber, B., Fischer, W.M., Gnanakaran, S., Yoon, H., Theiler, J., Abfalterer, W., Hengartner, N., Giorgi, E.E., Bhattacharya, T., Foley, B., et al. (2020). Tracking changes in SARS-CoV-2 Spike: evidence that D614G increases infectivity of the COVID-19 virus. Cell 182.
  3. Endo, A., Centre for the Mathematical Modelling of Infectious Diseases COVID-19 Working Group, Abbott, S., Kucharski, A.J., and Funk, S. (2020). Estimating the overdispersion in COVID-19 transmission using outbreak sizes outside China. Wellcome Open Res 5, 67.
  4. Hu, J., He, C.-L., Gao, Q.-Z., Zhang, G.-J., Cao, X.-X., Long, Q.-X., Deng, H.-J., Huang, L.-Y., Chen, J., Wang, K., et al. (2020). The D614G mutation of SARS-CoV-2 spike protein enhances viral infectivity and decreases neutralization sensitivity to individual convalescent sera. bioRxiv 2020.06.20.161323.
  5. Wagner, C., Roychoudhury, P., Hadfield, J., Hodcroft, E.B., Lee, J., Moncla, L.H., Müller, N.F., Behrens, C., Huang, M.-L., Mathias, P., et al. (2020). Comparing viral load and clinical outcomes in Washington State across D614G mutation in spike protein of SARS-CoV-2. Https://github.com/blab/ncov-D614G.

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“Repurposing” Off-patent Drugs offers big hopes of New Treatments

Reporter: Irina Robu, PhD

Given the substantial costs and the slow pace of drug discovery and development, repurposing old drugs has become a practice, partly because it involves the use of already developed compounds. Yet, there is lack of clinical interest in repurposing off patent drugs.

However, the scale of the opportunity for drug repurposing is huge. Initially approved for one disease, these drugs went off-patent and now show potential in other diseases. Even so, many non-profit groups see promise in supporting trials into drug repurposing. There is a huge untapped medicine chest of generic drugs with unexploited uses. These generic drugs are often cheap, already approved, off-patent and relatively quick to develop, whereas new drugs can cost millions of dollars to develop, test and 45% of the drugs fail in clinical trials.

However, numerous non-profit groups see potential in supporting trials into drug repurposing. Epidemiological data can offer enticing leads. Yet, clinical trials for these drugs are costly, but the benefits can be huge. The Drugs for Neglected Diseases Initiative, a Swiss non-profit research group, supported research into fexinidazole, which was abandoned by a pharma at an early stage. The drug showed to have antiparasitic qualities. However, after years of work in January 2020, it was approved for sleeping sickness in the Democratic Republic of Congo. It is the first oral medicine for the disease, and works for all stages of it.

Up till now, when it comes to cancer the most promising generic pills are known. Cancer Research, a UK based charity is testing aspirin to see if can stop cancer from recurring; metformin in a large prostate-cancer trial; and an anti-fungal medication to treat bowel cancer. At the same time, the Anticancer Fund in Brussels hopes that propranolol in treating cancers of the inner lining of blood vessels and pancreatic cancer. Propranolol is a generic 1960s beta-blocker used for a wide range of ailments such as hypertension, anxiety and migraine. If approved for cancer, its cost would be negligible in comparison the tens of thousands of dollars a month usually charged for cancer medicines.

Money seems the crucial constraint with these drugs, in addition to the clinical trials needed to have these drugs updated and relabeled. Only the makers or original developers of a drug are permitted to adjust its label. Sanofi, based in Paris, was the firm that requested regulatory review of fexinidazole for sleeping sickness, while the research was a charitable effort. But drug firms are not forced to support non-commercial efforts to repurpose drugs. And outside the industry it is tough to find the legal expertise to be able to do the  necessary paperwork.

As non-profits make progress in repurposing, corporate interest may be rising. In terms of achieving new treatment options, this is good news. But it will not bring cheaper medicines in areas traditionally neglected by the drug industry. Firms will focus on finding ways to patent the new uses and charge high prices for the finished product.

If governments need cheaper drugs, non-profits will need financial incentives and a cooperative regulatory framework. They include making regulators give free advice and waive approval fees, and a public fund to support repurposing. Yet, when drugs are approved, investors are paid back by the public health service, which makes savings by using the newly approved generic drugs.

SOURCE

https://www.economist.com/international/2019/02/28/repurposing-off-patent-drugs-offers-big-hopes-of-new-treatments?fsrc=scn/tw/te/bl/ed/crosspurposesrepurposingoffpatentdrugsoffersbighopesofnewtreatmentsinternational

 

Other related articles published in this Online Scientific Open Access Journal include:

 

The Castleman Disease Research Network publishes Phase 1 Results of Drug Repurposing Database for COVID-19

Reporter: Stephen J. Williams, PhD

https://pharmaceuticalintelligence.com/2020/06/27/the-castleman-disease-research-network-publishes-phase-1-results-of-drug-repurposing-database-for-covid-19/

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The Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV) Partnership on May 18, 2020: Leadership of AbbVie, Amgen, AstraZeneca, Bristol Myers Squibb, Eisai, Eli Lilly, Evotec, Gilead, GlaxoSmithKline, Johnson & Johnson, KSQ Therapeutics, Merck, Novartis, Pfizer, Roche, Sanofi, Takeda, and Vir. We also thank multiple NIH institutes (especially NIAID), the FDA, BARDA, CDC, the European Medicines Agency, the Department of Defense, the VA, and the Foundation for NIH

Reporter: Aviva Lev-Ari, PhD, RN

May 18, 2020

Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV) An Unprecedented Partnership for Unprecedented Times

JAMA. Published online May 18, 2020. doi:10.1001/jama.2020.8920

First reported in Wuhan, China, in December 2019, COVID-19 is caused by a highly transmissible novel coronavirus, SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2). By March 2020, as COVID-19 moved rapidly throughout Europe and the US, most researchers and regulators from around the world agreed that it would be necessary to go beyond “business as usual” to contain this formidable infectious agent. The biomedical research enterprise was more than willing to respond to the challenge of COVID-19, but it soon became apparent that much-needed coordination among important constituencies was lacking.

Clinical trials of investigational vaccines began as early as January, but with the earliest possible distribution predicted to be 12 to 18 months away. Clinical trials of experimental therapies had also been initiated, but most, except for a trial testing the antiviral drug remdesivir,2 were small and not randomized. In the US, there was no true overarching national process in either the public or private sector to prioritize candidate therapeutic agents or vaccines, and no efforts were underway to develop a clear inventory of clinical trial capacity that could be brought to bear on this public health emergency. Many key factors had to change if COVID-19 was to be addressed effectively in a relatively short time frame.

On April 3, leaders of the National Institutes of Health (NIH), with coordination by the Foundation for the National Institutes of Health (FNIH), met with multiple leaders of research and development from biopharmaceutical firms, along with leaders of the US Food and Drug Administration (FDA), the Biomedical Advanced Research and Development Authority (BARDA), the European Medicines Agency (EMA), and academic experts. Participants sought urgently to identify research gaps and to discuss opportunities to collaborate in an accelerated fashion to address the complex challenges of COVID-19.

These critical discussions culminated in a decision to form a public-private partnership to focus on speeding the development and deployment of therapeutics and vaccines for COVID-19. The group assembled 4 working groups to focus on preclinical therapeutics, clinical therapeutics, clinical trial capacity, and vaccines (Figure). In addition to the founding members, the working groups’ membership consisted of senior scientists from each company or agency, the Centers for Disease Control and Prevention (CDC), the Department of Veterans Affairs (VA), and the Department of Defense.

Figure.

Accelerating COVID-19 Therapeutic Interventions and Vaccines

ACTIV’s 4 working groups, each with one cochair from NIH and one from industry, have made rapid progress in establishing goals, setting timetables, and forming subgroups focused on specific issues (Figure). The goals of the working group, along with a few examples of their accomplishments to date, include the following.

 

The Preclinical Working Group was charged to standardize and share preclinical evaluation resources and methods and accelerate testing of candidate therapies and vaccines to support entry into clinical trials. The aim is to increase access to validated animal models and to enhance comparison of approaches to identify informative assays. For example, through the ACTIV partnership, this group aims to extend preclinical researchers’ access to high-throughput screening systems, especially those located in the Biosafety Level 3 (BSL3) facilities currently required for many SARS-CoV-2 studies. This group also is defining a prioritization approach for animal use, assay selection and staging of testing, as well as completing an inventory of animal models, assays, and BSL 3/4 facilities.

 

The Therapeutics Clinical Working Group has been charged to prioritize and accelerate clinical evaluation of a long list of therapeutic candidates for COVID-19 with near-term potential. The goals have been to prioritize and test potential therapeutic agents for COVID-19 that have already been in human clinical trials. These may include agents with either direct-acting or host-directed antiviral activity, including immunomodulators, severe symptom modulators, neutralizing antibodies, or vaccines. To help achieve these goals, the group has established a steering committee with relevant expertise and objectivity to set criteria for evaluating and ranking potential candidate therapies submitted by industry partners. Following a rigorous scientific review, the prioritization subgroup has developed a complete inventory of approximately 170 already identified therapeutic candidates that have acceptable safety profiles and different mechanisms of action. On May 6, the group presented its first list of repurposed agents recommended for inclusion in ACTIV’s master protocol for adaptive clinical trials. Of the 39 agents that underwent final prioritization review, the group identified 6 agents—including immunomodulators and supportive therapies—that it proposes to move forward into the master protocol clinical trial(s) expected to begin later in May.

 

The Clinical Trial Capacity Working Group is charged with assembling and coordinating existing networks of clinical trials to increase efficiency and build capacity. This will include developing an inventory of clinical trial networks supported by NIH and other funders in the public and private sectors, including contract research organizations. For each network, the working group seeks to identify their specialization in different populations and disease stages to leverage infrastructure and expertise from across multiple networks, and establish a coordination mechanism across networks to expedite trials, track incidence across sites, and project future capacity. The clinical trials inventory subgroup has already identified 44 networks, with access to adult populations and within domestic reach, for potential inclusion in COVID-19 trials. Meanwhile, the survey subgroup has developed 2 survey instruments to assess the capabilities and capacities of those networks, and its innovation subgroup has developed a matrix to guide deployment of innovative solutions throughout the trial life cycle.

 

The Vaccines Working Group has been charged to accelerate evaluation of vaccine candidates to enable rapid authorization or approval.4 This includes development of a harmonized master protocol for adaptive trials of multiple vaccines, as well as development of a trial network that could enroll as many as 100 000 volunteers in areas where COVID-19 is actively circulating. The group also aims to identify biomarkers to speed authorization or approval and to provide evidence to address cross-cutting safety concerns, such as immune enhancement. Multiple vaccine candidates will be evaluated, and the most promising will move to a phase 2/3 adaptive trial platform utilizing large geographic networks in the US and globally.5 Because time is of the essence, ACTIV will aim to have the next vaccine candidates ready to enter clinical trials by July 1, 2020.

References

1.

Desai  A .  Twentieth-century lessons for a modern coronavirus pandemic.   JAMA. Published online April 27, 2020. doi:10.1001/jama.2020.4165
ArticlePubMedGoogle Scholar

2.

NIH clinical trial shows remdesivir accelerates recovery from advanced COVID-19. National Institutes of Health. Published April 29, 2020. Accessed May 7, 2020. https://www.nih.gov/news-events/news-releases/nih-clinical-trial-shows-remdesivir-accelerates-recovery-advanced-covid-19

3.

NIH to launch public-private partnership to speed COVID-19 vaccine and treatment options. National Institutes of Health. Published April 17, 2020. Accessed May 7, 2020. https://www.nih.gov/news-events/news-releases/nih-launch-public-private-partnership-speed-covid-19-vaccine-treatment-options

4.

Corey  L , Mascola  JR , Fauci  AS , Collins  FS .  A strategic approach to COVID-19 vaccine R&D.   Science. Published online May 11, 2020. doi:10.1126/science.abc5312PubMedGoogle Scholar

5.

Angus  DC .  Optimizing the trade-off between learning and doing in a pandemic.   JAMA. Published online March 30, 2020. doi:10.1001/jama.2020.4984
ArticlePubMedGoogle Scholar

6.

Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV) portal. National Institutes of Health. Accessed May 15, 2020. https://www.nih.gov/ACTIV

7.

Accelerating Medicines Partnership (AMP). National Institutes of Health. Published February 4, 2014. Accessed May 7, 2020. https://www.nih.gov/research-training/accelerating-medicines-partnership-amp
SOURCE

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Live Notes, Real Time Conference Coverage 2020 AACR Virtual Meeting April 28, 2020 Symposium: New Drugs on the Horizon Part 3 12:30-1:25 PM

Reporter: Stephen J. Williams, PhD

New Drugs on the Horizon: Part 3
Introduction

Andrew J. Phillips, C4 Therapeutics

  • symposium brought by AACR CICR and had about 30 proposals for talks and chose three talks
  • unfortunately the networking event is not possible but hope to see you soon in good health

ABBV-184: A novel survivin specific T cell receptor/CD3 bispecific therapeutic that targets both solid tumor and hematological malignancies

Edward B Reilly
AbbVie Inc. @abbvie

  • T-cell receptors (TCR) can recognize the intracellular targets whereas antibodies only recognize the 25% of potential extracellular targets
  • survivin is expressed in multiple cancers and correlates with poor survival and prognosis
  • CD3 bispecific TCR to survivn (Ab to CD3 on T- cells and TCR to survivin on cancer cells presented in MHC Class A3)
  • ABBV184  effective in vivo in lung cancer models as single agent;
  • in humanized mouse tumor models CD3/survivin bispecific can recruit T cells into solid tumors; multiple immune cells CD4 and CD8 positive T cells were found to infiltrate into tumor
  • therapeutic window as measured by cytokine release assays in tumor vs. normal cells very wide (>25 fold)
  • ABBV184 does not bind platelets and has good in vivo safety profile
  • First- in human dose determination trial: used in vitro cancer cell assays to determine 1st human dose
  • looking at AML and lung cancer indications
  • phase 1 trial is underway for safety and efficacy and determine phase 2 dose
  • survivin has very few mutations so they are not worried about a changing epitope of their target TCR peptide of choice

The discovery of TNO155: A first in class SHP2 inhibitor

Matthew J. LaMarche
Novartis @Novartis

  • SHP2 is an intracellular phosphatase that is upstream of MEK ERK pathway; has an SH2 domain and PTP domain
  • knockdown of SHP2 inhibits tumor growth and colony formation in soft agar
  • 55 TKIs there are very little phosphatase inhibitors; difficult to target the active catalytic site; inhibitors can be oxidized at the active site; so they tried to target the two domains and developed an allosteric inhibitor at binding site where three domains come together and stabilize it
  • they produced a number of chemical scaffolds that would bind and stabilize this allosteric site
  • block the redox reaction by blocking the cysteine in the binding site
  • lead compound had phototoxicity; used SAR analysis to improve affinity and reduce phototox effects
  • was very difficult to balance efficacy, binding properties, and tox by adjusting stuctures
  • TNO155 is their lead into trials
  • SHP2 expressed in T cells and they find good combo with I/O with uptick of CD8 cells
  • TNO155 is very selective no SHP1 inhibition; SHP2 can autoinhibit itself when three domains come together and stabilize; no cross reactivity with other phosphatases
  • they screened 1.5 million compounds and got low hit rate so that is why they needed to chemically engineer and improve on the classes they found as near hits

Closing Remarks

 

Xiaojing Wang
Genentech, Inc. @genentech

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Live Notes, Real Time Conference Coverage 2020 AACR Virtual Meeting April 27, 2020 Opening Remarks and Clinical Session 11:45am-1:15pm Advances in Cancer Drug Discovery

SESSION VMS.CH01.01 – Advances in Cancer Drug Design and Discovery

April 27, 2020, 11:45 AM – 1:15 PM
Virtual Meeting: All Session Times Are U.S. EDT
DESCRIPTIONAll session times are U.S. Eastern Daylight Time (EDT).

Session Type
Virtual Minisymposium
Track(s)
Cancer Chemistry
14 Presentations
11:45 AM – 11:45 AM
– ChairpersonZoran Rankovic. St. Jude Children’s Research Hospital, Memphis, TN

11:45 AM – 11:45 AM
– ChairpersonChristopher G. Nasveschuk. C4 Therapeutics, Watertown, MA

11:45 AM – 11:50 AM
– IntroductionZoran Rankovic. St. Jude Children’s Research Hospital, Memphis, TN

11:50 AM – 12:00 PM
1036 – Discovery of a highly potent, efficacious and orally active small-molecule inhibitor of embryonic ectoderm development (EED)Changwei Wang, Rohan Kalyan Rej, Jianfeng Lu, Mi Wang, Kaitlin P. Harvey, Chao-Yie Yang, Ester Fernandez-Salas, Jeanne Stuckey, Elyse Petrunak, Caroline Foster, Yunlong Zhou, Rubin Zhou, Guozhi Tang, Jianyong Chen, Shaomeng Wang. Rogel Cancer Center and Departments of Internal Medicine, Pharmacology, and Medicinal Chemistry, Life Sciences Institute, University of Michigan, Ann Arbor, MI, Ascentage Pharma Group, Taizhou, Jiangsu, China

12:00 PM – 12:05 PM
– Discussion

12:05 PM – 12:15 PM
1037 – Orally available small molecule CD73 inhibitor reverses immunosuppression through blocking of adenosine productionXiaohui Du, Brian Blank, Brenda Chan, Xi Chen, Yuping Chen, Frank Duong, Lori Friedman, Tom Huang, Melissa R. Junttila, Wayne Kong, Todd Metzger, Jared Moore, Daqing Sun, Jessica Sun, Dena Sutimantanapi, Natalie Yuen, Tatiana Zavorotinskaya. ORIC Pharmaceuticals, South San Francisco, CA, ORIC Pharmaceuticals, South San Francisco, CA, ORIC Pharmaceuticals, South San Francisco, CA, ORIC Pharmaceuticals, South San Francisco, CA

12:15 PM – 12:20 PM
– Discussion

12:20 PM – 12:30 PM
1038 – A potent and selective PARP14 inhibitor decreases pro-tumor macrophage function and elicits inflammatory responses in tumor explantsLaurie Schenkel, Jennifer Molina, Kerren Swinger, Ryan Abo, Danielle Blackwell, Anne Cheung, William Church, Kristy Kuplast-Barr, Alvin Lu, Elena Minissale, Mario Niepel, Melissa Vasbinder, Tim Wigle, Victoria Richon, Heike Keilhack, Kevin Kuntz. Ribon Therapeutics, Cambridge, MA

12:30 PM – 12:35 PM
– Discussion

12:35 PM – 12:45 PM
1039 – Fragment-based drug discovery to identify small molecule allosteric inhibitors of SHP2. Philip J. Day, Valerio Berdini, Juan Castro, Gianni Chessari, Thomas G. Davies, James E. H. Day, Satoshi Fukaya, Chris Hamlett, Keisha Hearn, Steve Hiscock, Rhian Holvey, Satoru Ito, Yasuo Kodama, Kenichi Matsuo, Yoko Nakatsuru, Nick Palmer, Amanda Price, Tadashi Shimamura, Jeffrey D. St. Denis, Nicola G. Wallis, Glyn Williams, Christopher N. Johnson. Astex Pharmaceuticals, Inc., Cambridge, United Kingdom, Taiho Pharmaceutical Co., Ltd, Tsukuba, Japan

Abstract: The ubiquitously expressed protein tyrosine phosphatase SHP2 is required for signalling downstream of receptor tyrosine kinases (RTKs) and plays a role in regulating many cellular processes. Recent advances have shown that genetic knockdown and pharmacological inhibition of SHP2 suppresses RAS/MAPK signalling and inhibits proliferation of RTK-driven cancer cell lines. SHP2 is now understood to act upstream of RAS and plays a role in KRAS-driven cancers, an area of research which is rapidly growing. Considering that RTK deregulation often leads to a wide range of cancers and the newly appreciated role of SHP2 in KRAS-driven cancers, SHP2 inhibitors are therefore a promising therapeutic approach.
SHP2 contains two N-terminal tandem SH2 domains (N-SH2, C-SH2), a catalytic phosphatase domain and a C-terminal tail. SHP2 switches between “open” active and “closed” inactive forms due to autoinhibitory interactions between the N-SH2 domain and the phosphatase domain. Historically, phosphatases were deemed undruggable as there had been no advancements with active site inhibitors. We hypothesised that fragment screening would be highly applicable and amenable to this target to enable alternative means of inhibition through identification of allosteric binding sites. Here we describe the first reported fragment screen against SHP2.
Using our fragment-based PyramidTM approach, screening was carried out on two constructs of SHP2; a closed autoinhibited C-terminal truncated form (phosphatase and both SH2 domains), as well as the phosphatase-only domain. A combination of screening methods such as X-ray crystallography and NMR were employed to identify fragment hits at multiple sites on SHP2, including the tunnel-like allosteric site reported by Chen et al, 2016. Initial fragment hits had affinities for SHP2 in the range of 1mM as measured by ITC. Binding of these hits was improved using structure-guided design to generate compounds which inhibit SHP2 phosphatase activity and are promising starting points for further optimization.

  • anti estrogen receptor therapy: ER degraders is one class
  • AZ9833 enhances degradation of ER alpha
  • worked in preclinical mouse model (however very specific)
  • PK parameters were good for orally available in rodents;  also in vitro and in vivo correlation correlated in rats but not in dogs so they were not sure if good to go in humans
  • they were below Km in rats but already at saturated in dogs, dogs were high clearance
  • predicted human bioavailability at 40%

 

12:45 PM – 12:50 PM
– Discussion

12:50 PM – 1:00 PM
1042 – Preclinical pharmacokinetic and metabolic characterization of the next generation oral SERD AZD9833Eric T. Gangl, Roshini Markandu, Pradeep Sharma, Andy Sykes, Petar Pop-Damkov, Pablo Morentin Gutierrez, James S. Scott, Dermot F. McGinnity, Adrian J. Fretland, Teresa Klinowska. AstraZeneca, Waltham, MA

1:00 PM – 1:05 PM
– Discussion

1:05 PM – 1:15 PM
– Closing RemarksChristopher G. Nasveschuk. MA

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