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
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
Novartis’ Kymriah (tisagenlecleucel), FDA approved genetically engineered immune cells, would charge $475,000 per patient, will use Programs that Payers will pay only for Responding Patients
Curator: Aviva Lev-Ari, PhD, RN
UPDATED on 9/27/2016
Kite Pharma ($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.
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
THOUSAND OAKS, Calif., Sept. 27, 2016 /PRNewswire/ — Amgen (NASDAQ:AMGN) today announced top-line results of the Phase 3 CLARION trial, which evaluated an investigational regimen of KYPROLIS® (carfilzomib), melphalan and prednisone (KMP) versus Velcade® (bortezomib), melphalan and prednisone (VMP) for 54 weeks in patients with newly diagnosed multiple myeloma who were ineligible for hematopoietic stem-cell transplant. The trial did not meet the primary endpoint of superiority in progression-free survival (PFS) (median PFS 22.3 months for KMP versus 22.1 months for VMP, HR = 0.91, 95 percent CI, 0.75 – 1.10). While the data for overall survival, a secondary endpoint, are not yet mature, the observed hazard ratio (KMP versus VMP) was 1.21 (95 percent CI, 0.90 – 1.64). Neither result was statistically significant.
Overall, the adverse events in the KMP arm were consistent with the known safety profile of KYPROLIS. The incidence of Grade 3 or higher adverse events was 74.7 percent in the KMP arm and 76.2 percent in the VMP arm. Fatal treatment-emergent adverse events occurred in 6.5 percent of KMP patients and 4.3 percent of VMP patients. The incidence of Grade 2 or higher peripheral neuropathy, a secondary endpoint, was 2.5 percent in the KMP arm and 35.1 percent in the VMP arm.
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
Immune-Oncology Molecules In Development consist of the following four Classes of Drugs:
- 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 inDevelop-ment |
Checkpoint InhibitorsDrug/Pharma |
Co-Stimulatory AgentsDrug/Pharma |
ImmunomodulatorsDrug/Pharma |
5th generation CAR SignalingPharma/PartnersListed asDrug (Target/disease indication) |
Pre-Clinical |
REGN2810/RegeneronPD-1/AgenusAnti-Lag3/Tesaro, AnaptyBioIMP701/Prima BioMedLAG3/Agenus, IncyteLag3/MerckAnti-TIM3/BristolAnti-TIM3/Tesaro, AnaptyBioAnti-TIM3/Agenus |
OX40/AmgenGITR/BristolGITR/PfizerFPA154/Five PrimeAnti-GITR/TG TherapeuticsAnti-GITR/Incyte |
CTLA4/AgenusIDO1/Pfizer,iTEOSF001287/Bristol,FlexusIMA942/RocheVIBR/Pfizer |
Kite Pharma/AmgenMultiple targets/ hematologic & solid tumorsBellicum PharmaBPX-401 (CD19/leukemia)BPX-601 (PSCA/prostate)BPX-701 (PRAME/melanomaCellectis/PfizerCornel/Ohio StateUCART123 (CD123/AML)UCARTCS1 (CD38/multiple myeloma)UCART 38 (CD38 /multiple myeloma)UCART 22 ( CD22/ALL)Juno Therapeutics/CellgeneMUC116 (IL12/ovarian)ROR1 (ROR1/B-ALL)Univ. of Penna/NovartisCAR-T hPSMA (PSMA/prostate) |
Phase I |
BMS986016/Bristol |
Urelumab/ BristolMyersMEDI-0562/ AstraZenecaRG7888/RocheOX40/AgonoxOX40/GSKMK-4166/MerckSEA-CD40/Seattle GeneticsCD40/Roche |
Anti-CEA Il2v/RocheFPA008/Bristol, Five PrimeLY3022855/LillyAMG820/AmgenARRY382/Array, Celgene |
Ziopharm/Intrexon/ MD AndersonCD19 (CD19/B-ALL)Kite Pharma/AmgenKTE-C19 (ZUMA-3/Adult ALL)KTE-C19 (ZUMA-4/pediatric ALL)EGFRvII (EGFR/glioblastoma)Bluebird Bio/Cellgene/Baylorbb2121 (BCMA/B-ALL)Juno Therapeutics/CellgeneJCAR017 (CD19/leukemias)JCAR014 (CD19/NHLymphoma) |
Phase I/II |
MEDI0680/AstraZenec |
PF-05082566/PfizerVarilumab/Celldex, Bristol-Myers |
NKG2A/Innate,AstraZen.dCellVax/BioMatrixAPN301/Apeiron, MerckKGA |
Juno Therapeutics/CellgeneJCAR015 (CD19/ALL)JTCR016 (WT-1/AML,CML) |
Phase II |
Pidlizumab/MedivationAvelumab/Pfizer, MerckKGa |
Lirilumab/BMY/InnateEpacadostat/Incyte, MerckGDC-0919/NewLinkGenetics, RocheTG4010/Transgene S.A.Ontak/Esai, Lilly, TevaDenenicokin/Bristol, NovoNordiskPLX3397/Plexikon, MerckMCS110/NovartisJNJ40346527/JNJT-Vec/AmgenEmactuzumab/Roche |
Univ. of Penna/NovartisCTL019 (CD19/leukemia)Kite Pharma/AmgenKTE-C19 (ZUMA-1/leukemia)KTE-C19 (ZUMA-2/mantle cell leukemia) |
|
Phase III |
Duvalumab/AstraZencaAtezolizumab/Roche |
Tremelimumab/AstraZeneca |
||
Approved |
Opdivo/Bristol-MyersKeytruda/Merck |
Yervoy/Bristol-Myers |
Part II:
Articles on CTLA4 @ pharmaceuticalintelligence.com
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
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
Curator: Larry H. Bernstein, MD, FCAP
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
Reporter: Aviva Lev-Ari, PhD, RN
Novel biomarkers for targeting cancer immunotherapy
Curator: Larry H. Bernstein, MD, FCAP
Reporter: Aviva Lev-Ari, PhD, RN
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.
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
Curator & Reporter: Larry H. Bernstein, MD, FCAP
Reporter: Aviva Lev-Ari, PhD, RN
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This is very insightful. There is no doubt that there is the bias you refer to. 42 years ago, when I was postdocing in biochemistry/enzymology before completing my residency in pathology, I knew that there were very influential mambers of the faculty, who also had large programs, and attracted exceptional students. My mentor, it was said (although he was a great writer), could draft a project on toilet paper and call the NIH. It can’t be true, but it was a time in our history preceding a great explosion. It is bizarre for me to read now about eNOS and iNOS, and about CaMKII-á, â, ã, ä – isoenzymes. They were overlooked during the search for the genome, so intermediary metabolism took a back seat. But the work on protein conformation, and on the mechanism of action of enzymes and ligand and coenzyme was just out there, and became more important with the research on signaling pathways. The work on the mechanism of pyridine nucleotide isoenzymes preceded the work by Burton Sobel on the MB isoenzyme in heart. The Vietnam War cut into the funding, and it has actually declined linearly since.
A few years later, I was an Associate Professor at a new Medical School and I submitted a proposal that was reviewed by the Chairman of Pharmacology, who was a former Director of NSF. He thought it was good enough. I was a pathologist and it went to a Biochemistry Review Committee. It was approved, but not funded. The verdict was that I would not be able to carry out the studies needed, and they would have approached it differently. A thousand young investigators are out there now with similar letters. I was told that the Department Chairmen have to build up their faculty. It’s harder now than then. So I filed for and received 3 patents based on my work at the suggestion of my brother-in-law. When I took it to Boehringer-Mannheim, they were actually clueless.