Leaders in Pharmaceutical Business Intelligence (LPBI) Group

Immune-Oncology Molecules In Development & Articles on Topic in @pharmaceuticalintelligence.com

Curators: Stephen J Williams, PhD and Aviva Lev-Ari, PhD, RN

 

 

UPDATED on 10/2/2018

2018 Nobel Prize in Physiology or Medicine for contributions to Cancer Immunotherapy to James P. Allison, Ph.D., of the University of Texas, M.D. Anderson Cancer Center, Houston, Texas. Dr. Allison shares the prize with Tasuku Honjo, M.D., Ph.D.,of Kyoto University Institute, Japan

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2018/10/01/2018-nobel-prize-in-physiology-or-medicine-for-contributions-to-cancer-immunotherapy-to-james-p-allison-ph-d-of-the-university-of-texas-m-d-anderson-cancer-center-houston-texas-dr-allison-sh/

 

UPDATED on 9/5/2017

FDA has approved the world’s first CAR-T therapy, Novartis for Kymriah (tisagenlecleucel) and Gilead’s $12 billion buy of Kite Pharma, no approved drug and Canakinumab for Lung Cancer (may be?)

Curator: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2017/08/30/fda-has-approved-the-worlds-first-car-t-therapy-novartis-for-kymriah-tisagenlecleucel-and-gileads-12-billion-buy-of-kite-pharma-no-approved-drug-and-canakinumab-for-lung-cancer-may-be/

Novartis’ Kymriah (tisagenlecleucel), FDA approved genetically engineered immune cells, would charge $475,000 per patient, will use Programs that Payers will pay only for Responding Patients

Curator: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2017/08/31/novartis-kymriah-tisagenlecleucel-fda-approved-genetically-engineered-immune-cells-would-charge-475000-per-patient-will-use-programs-that-payers-will-pay-only-for-responding-patients/ 

UPDATED on 9/27/2016

Kite Pharma ($KITE) climbs after Phase II data tee up FDA filing for CAR-T

Kite Pharma ($KITE) has posted an interim analysis of Phase II CAR-T data it thinks are strong enough to support regulatory approval. The CAR-T triggered complete remissions in 47% of patients with an aggressive form of non-Hodgkin lymphoma (NHL), although a dropoff in the number of responders over the first three months has raised questions about durability.

At the time of the interim analysis, Kite had administered its CD19-targeting CAR-T to 51 patients with chemorefractory diffuse large B-cell lymphoma (DLBCL). More than three quarters of patients experienced an objective response. Close to half experienced complete remission. When paired to stronger data from a small group of patients with transformed follicular lymphoma (TFL) and primary mediastinal B-cell lymphoma (PMBCL), Kite thinks the interim analysis boosts its prospects.

http://www.fiercebiotech.com/biotech/kite-climbs-after-phii-data-tee-up-fda-filing-for-car-t?utm_medium=nl&utm_source=internal&mrkid=993697&mkt_tok=eyJpIjoiTURRM1pXWmpNVFZtTjJFMyIsInQiOiJmUmp3NlJKbVluZFYxWHQrQkxyblR6Njh3Q3lSa0dFVVRcL3pzdmNrZERPa091QWp2OXBWNnBwc1NnMWJqSDNjbHRUNTFDZnl3QWxQQUxubUNoQnlwNmNJengwOE9wUXNZSUNjT00yenNsY2s9In0%3D

 

UPDATED on 9/27/2016

Amgen Announces Top-Line Results From Phase 3 KYPROLIS® (Carfilzomib) CLARION Study In Newly Diagnosed Multiple Myeloma Patients

Amgen to Hold Analyst Call Today at 8:30 a.m. ET

http://www.amgen.com/media/news-releases/2016/09/amgen-announces-topline-results-from-phase-3-kyprolis-carfilzomib-clarion-study-in-newly-diagnosed-multiple-myeloma-patients/

UPDATED on 6/8/2016

Cancer researchers see promise in giving patients combinations of multiple drugs that are proving more effective than one or two. But the strategy poses a dilemma for health insurers and patients: even higher prices.

Combination Drug Therapies for Cancer Show Promise at Higher Potential Cost

‘Group discounts’ suggested as one means of cutting cost of medicines in a combination regimen

SOURCE

http://www.wsj.com/articles/combination-drug-therapies-for-cancer-show-promise-at-higher-potential-cost-1465141936

 

 

Immune-Oncology Molecules In Development consist of the following four Classes of Drugs:

1.    Checkpoint Inhibitors

• PD-1
• PD-L1 (Programmed Death (PD)) 
• LAG-3
• TIM-3

 

2.    Co-Stimulatory Agents

• CD137/41BB
• OX40
• CD27
• GITR
• CD40

 

3.    Immunomodulators

• CTLA4 (cytotoxic T Lymphocyte Associated protein-4)
• KIR
• IDO IL-2
• IL-21
• CSF1R
• Vaccines

SOURCE: Page 66 in

http://jpmorgan.metameetings.com/confbook/healthcare16/stash/misc/IO%20Combos.pdf

AND

4.    5th generation CAR Signaling

• CAR-T (chimeric antigen receptor T- cell)

T cells are genetically engineered to produce special receptors on their surface called chimeric antigen receptors (CARs).

PART I:

Immune-Oncology Molecules In Development

 

Anti-Cancer – Four Drug Classes of Immune-Oncology Molecules in Development, including CAR-T

Curator: Stephen J Williams, PhD

 For a bigger version of this table in Word please click on the below file:

Table JPM2016 ImmuneTherapy in Development

Phase in Develop- ment	Checkpoint Inhibitors Drug/Pharma	Co-Stimulatory Agents Drug/Pharma	Immunomodulators Drug/Pharma	5th generation CAR Signaling Pharma/Partners Listed as Drug (Target/disease indication)
Pre-Clinical	REGN2810/Regeneron PD-1/Agenus Anti-Lag3/Tesaro, AnaptyBio IMP701/Prima BioMed LAG3/Agenus, Incyte Lag3/Merck Anti-TIM3/Bristol Anti-TIM3/Tesaro, AnaptyBio Anti-TIM3/Agenus	OX40/Amgen GITR/Bristol GITR/Pfizer FPA154/Five Prime Anti-GITR/TG Therapeutics Anti-GITR/Incyte	CTLA4/Agenus IDO1/Pfizer,iTEOS F001287/Bristol,Flexus IMA942/Roche VIBR/Pfizer	Kite Pharma/Amgen Multiple targets/ hematologic & solid tumors Bellicum Pharma BPX-401 (CD19/leukemia) BPX-601 (PSCA/prostate) BPX-701 (PRAME/melanoma Cellectis/PfizerCornel/Ohio State UCART123 (CD123/AML) UCARTCS1 (CD38/multiple myeloma) UCART 38 (CD38 /multiple myeloma) UCART 22 ( CD22/ALL) Juno Therapeutics/Cellgene MUC116 (IL12/ovarian) ROR1 (ROR1/B-ALL) Univ. of Penna/Novartis CAR-T hPSMA (PSMA/prostate)
Phase I	BMS986016/Bristol	Urelumab/ BristolMyers MEDI-0562/ AstraZeneca RG7888/Roche OX40/Agonox OX40/GSK MK-4166/Merck SEA-CD40/Seattle Genetics CD40/Roche	Anti-CEA Il2v/Roche FPA008/Bristol, Five Prime LY3022855/Lilly AMG820/Amgen ARRY382/Array, Celgene	Ziopharm/Intrexon/ MD Anderson CD19 (CD19/B-ALL) Kite Pharma/Amgen KTE-C19 (ZUMA-3/Adult ALL) KTE-C19 (ZUMA-4/pediatric ALL) EGFRvII (EGFR/glioblastoma) Bluebird Bio/Cellgene/Baylor bb2121 (BCMA/B-ALL) Juno Therapeutics/Cellgene JCAR017 (CD19/leukemias) JCAR014 (CD19/NHLymphoma)
Phase I/II	MEDI0680/AstraZenec	PF-05082566/Pfizer Varilumab/Celldex, Bristol-Myers	NKG2A/Innate,AstraZen. dCellVax/BioMatrix APN301/Apeiron, MerckKGA	Juno Therapeutics/Cellgene JCAR015 (CD19/ALL) JTCR016 (WT-1/AML,CML)
Phase II	Pidlizumab/Medivation Avelumab/Pfizer, MerckKGa		Lirilumab/BMY/Innate Epacadostat/Incyte, Merck GDC-0919/NewLinkGenetics, Roche TG4010/Transgene S.A. Ontak/Esai, Lilly, Teva Denenicokin/Bristol, NovoNordisk PLX3397/Plexikon, Merck MCS110/Novartis JNJ40346527/JNJ T-Vec/Amgen Emactuzumab/Roche	Univ. of Penna/Novartis CTL019 (CD19/leukemia) Kite Pharma/Amgen KTE-C19 (ZUMA-1/leukemia) KTE-C19 (ZUMA-2/mantle cell leukemia)
Phase III	Duvalumab/AstraZenca Atezolizumab/Roche		Tremelimumab/AstraZeneca
Approved	Opdivo/Bristol-Myers Keytruda/Merck		Yervoy/Bristol-Myers

 

Part II:

Articles on CTLA4 @ pharmaceuticalintelligence.com

Cancer Immunotherapy

Curator: Larry H. Bernstein, MD, FCAP

Combined anti-CTLA4 and anti-PD1 immunotherapy shows promising results against advanced melanoma

Reporter: Aviva Lev-Ari, PhD, RN

Pfizer bets $1 billion on BioAtla Conditionally Active Biologics | BioAcceleration™ for Protein Therapeutics

Reporter: Aviva Lev-Ari, PhD, RN

Gene expression and adaptive immune resistance mechanisms in lymphoma

Curator: Larry H Bernstein, MD, FCAP

The Delicate Connection: IDO (Indolamine 2, 3 dehydrogenase) and Cancer Immunology

Author and Curator: Demet Sag, PhD, CRA, GCP    

Pancreatic Cancer: Genetics, Genomics and Immunotherapy

Author: Tilda Barliya, PhD

 

Articles on ‘PD-L1’ @ pharmaceuticalintelligence.com

 

Myc and Cancer Resistance

Curator: Larry H. Bernstein, MD, FCAP

 

Merck and Pfizer Announces Global Strategic Alliance on Anti-PD-L1 to Accelerate Presence in Immuno-Oncology

Reporter: Aviva Lev-Ari, PhD, RN

Immuno-Oncology Combination Therapy: Implications For Major Pharma

Reporter: Aviva Lev-Ari, PhD, RN

PD1 Inhibitor atezolizumab may show promise in bladder cancer in patients with high PDL1 expression

Reporter: Stephen J Williams

In Cancer Volume 2 Melanoma

Cancer Immunotherapy Conference & Biomarkers for Cancer Immunotherapy Symposium, March 6-11, 2016 | Moscone North Convention Center | San Francisco, CA

Reporter: Aviva Lev-Ari, PhD, RN

Novel biomarkers for targeting cancer immunotherapy

Curator: Larry H. Bernstein, MD, FCAP

Metastatic Melanoma: Immunotherapy Drug Combination, Ipilimumab plus Nivolumab – Shrinks Tumor Size In 58% Skin Cancer Patients

Reporter: Aviva Lev-Ari, PhD, RN

New Findings in Endometrial Cancer: Mutations, Molecular Types and Immune Responses Evoked by Mutation-prone Endometrial, Ovarian Cancer Subtypes

Curator: Aviva Lev-Ari, PhD, RN

Articles on ‘CAR-T’ @ pharmaceuticalintelligence.com

Leaders in the CAR-T Field Are Proceeding With Cautious Hope

Reporter: Stephen J. Williams, Ph.D.

CAR-T therapy in leukemia

Curator: Larry H. Bernstein, MD, FCAP

In Cancer Volume 2 Steroids, Inflammation, and CAR-T Therapy

In Cancer Volume 2 NIH Considers Guidelines for CAR-T therapy: Report from Recombinant DNA Advisory Committee

Rosa’s to like

Curator & Reporter: Larry H. Bernstein, MD, FCAP

Juno’s approach eradicated cancer cells in 10 of 12 leukemia patients, indicating potential to transform the standard of care in oncology

Reporter: Aviva Lev-Ari, PhD, RN