On December 7, 2020 Jubilant Therapeutics Inc., a biopharmaceutical company advancing small molecule modulators to address unmet medical needs in oncology and autoimmune diseases, reported efficacy data from a study of JBI-802, its novel dual inhibitor of LSD1-HDAC6, in multiple acute myeloid leukemia (AML) models, and the identification of novel, undisclosed biomarkers that will aid in patient stratification (Press release, Jubilant Therapeutics, DEC 7, 2020, View Source [SID1234572383]). The data, presented today in a poster session at the 62nd American Society of Hematology (ASH) (Free ASH Whitepaper) Virtual Annual Meeting, demonstrate superior efficacy in select AML models as compared to single agent inhibitors, with a unique mechanism of action.

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"We are highly encouraged to verify that both LSD1 and HDAC6 mechanisms are operational with JBI-802 and the dual inhibition shows a stronger and more potent effect than the standalone inhibitors. We are also excited about the potential biomarkers we have identified specifically for the dual inhibitor which will be highly valuable in identifying sensitive patient populations," said Syed Kazmi, President and Chief Executive Officer of Jubilant Therapeutics. "We believe JBI-802 could one day serve as a powerful therapeutic agent for the treatment of specific cancers, including myelodysplastic syndrome (MDS), select acute myeloid leukemia (AML) and solid tumor subsets."

A link to the abstract, Novel Dual Inhibitor of LSD1-HDAC6/8 for Treatment of Cancer, is available through the ASH (Free ASH Whitepaper) conference website.

Key highlights from the study of JBI-802 as compared to single agent LSD1 or HDAC6 selective inhibitors in AML models show:

Both LSD1 and HDAC6 mechanisms are operational with JBI-802 resulting in stronger anti-proliferation and efficacy in a subset of cell lines;
Selective biomarkers are modulated with the dual inhibition of JBI-802 not seen by the single agent inhibitors, leading to the potential for patient stratification and the evaluation of treatment response; and
JBI-802 has a superior efficacy, safety and tolerability profile.

On December 7, 2020 Allogene Therapeutics, Inc. (Nasdaq: ALLO), a clinical-stage biotechnology company pioneering the development of allogeneic CAR T (AlloCAR T) therapies for cancer, reported preclinical findings of ALLO-605, the Company’s first TurboCAR clinical candidate and next-generation AlloCAR T therapy for relapsed or refractory multiple myeloma, will be presented in a poster session today at the 62nd Annual Meeting of the American Society of Hematology (ASH) (Free ASH Whitepaper) (Press release, Allogene, DEC 7, 2020, View Source [SID1234572474]).

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Allogene developed the TurboCAR technology to further enhance the potency of cell therapies. This technology allows ligand independent, cytokine signaling to be engineered selectively into CAR T cells. TurboCARs have the potential to enhance AlloCAR T cell proliferation and overcome T cell exhaustion. The technology is being deployed initially as part of the Company’s three-pronged approach to targeting BCMA in patients with multiple myeloma. Results from the preclinical studies demonstrated that ALLO-605 showed enhanced cytokine secretion, polyfunctionality, improved serial killing activity in vitro, and enhanced eradication of tumors in animal models of myeloma.

"Allogene continues to innovate across our AlloCAR T platform with next generation technologies that can be applied to multiple programs," said Rafael Amado, M.D., Executive Vice President of Research & Development and Chief Medical Officer of Allogene. "The advances with TurboCAR not only support our approach to targeting BCMA, but also allow us to potentially enhance the activity of other AlloCAR T candidates. We are eager to bring ALLO-605 into the clinic and anticipate filing our first IND utilizing this novel technology in the first half of 2021."

In a highly aggressive orthotopic mouse model of multiple myeloma, ALLO-605 demonstrated an increase in peak expansion and persistence compared to standard BCMA CAR T cells, resulting in rapid and durable antitumor responses. No bone marrow or extramedullary relapses were seen in mice treated with ALLO-605 which resulted in increased survival. The expansion and persistence of ALLO-605 was dependent upon BCMA expression on the target cells and there was no evidence of TurboCAR T cell expansion in the absence of target engagement.

On December 7, 2020 SELLAS Life Sciences Group, Inc. (Nasdaq: SLS) ("SELLAS"), a late-stage clinical biopharmaceutical company focused on the development of novel cancer immunotherapies for a broad range of cancer indications, and 3D Medicines Inc. ("3DMed"), a China-based biopharmaceutical company developing next-generation immuno-oncology drugs, reported that they have entered into an Exclusive License Agreement granting rights to 3DMed to develop and commercialize SELLAS’ lead late-stage clinical candidate, galinpepimut-S (GPS), as well as its next generation heptavalent immunotherapeuatic, GPS+, which is at preclinical stage, across all therapeutic and diagnostic uses in the Greater China territory (mainland China, Hong Kong, Macau and Taiwan) (Press release, Sellas Life Sciences, DEC 7, 2020, View Source [SID1234572315]). SELLAS retains sole rights to GPS and GPS+ outside of the Greater China area. Potential payments to SELLAS under the agreement could total $202 million in license fees and milestone payments, not including future royalties.

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GPS is an innovative potentially first-in-class WT1-targeting artificially engineered synthetic heteroclitic immunotherapeutic in development for hematological malignancies and solid tumors characterized by an overexpression of the WT1 (Wilms Tumor Protein) antigen. In 2020, SELLAS commenced a Phase 3 clinical trial (the REGAL study) of GPS in patients with acute myeloid leukemia (AML) who have reached second complete remission.

"This agreement represents an important achievement for SELLAS as we continue to progress our clinical development program for GPS. We are excited to collaborate with 3DMed on the development and commercialization of GPS in China. 3DMed, an ambitious biopharmaceutical company with development, registration and commercialization capabilities with a focus on developing next-generation immuno-oncology drugs and an experienced team, is a wonderfully complementary partner in bringing the potential of GPS to patients in Greater China. The collaboration begins to put in place essential elements designed to expand the reach of GPS outside the United States, following potential regulatory approvals," said Angelos Stergiou, MD, ScD h.c., President and Chief Executive Officer of SELLAS. "The completion of this agreement, amid the COVID-19 pandemic, shows the execution strength of our team. We are also pleased to have strengthened our balance sheet with the non-dilutive upfront license fee of $7.5 million with other potential milestones over the next several months."

"We are very pleased to execute this exclusive license agreement of GPS and GPS+ in the Greater China area with SELLAS," said John Gong, M.D., Ph.D., Chairman and Chief Executive Officer of 3DMed. "GPS and GPS+ are innovative therapeutics and, with growing need for new treatments, GPS’ potential use as a monotherapy as well as in combination with our Envafolimab, an innovative subcutaneous PD-L1 antibody which we have just filed for marketing approval in China, could create significant value for both 3DMed and SELLAS. This partnership highly reflects the vision of 3DMed to help patients with cancer to live longer and better. We believe that the addition of the GPS and GPS+ assets to our clinical portfolio is an important synergistic and strategic step for 3DMed as this partnership will expand our company’s therapeutic area expertise and improve our competitiveness."

Under the financial terms of the agreement:

SELLAS could potentially receive up to $202 million in license and milestone payments during the course of the collaboration, not including future royalties.

SELLAS will receive payment of an upfront license fee of $7.5 million payable this quarter and is eligible to receive potential near-term milestones totaling up to an additional $8.0 million.

SELLAS is entitled to receive royalties on Chinese sales on a tiered basis, dependent on sales levels, ranging from the high single to low double-digit percentage.

3DMed will be responsible for the costs of all development and regulatory activity for Greater China.
Torreya acted as a financial advisor to SELLAS.

About Galinpepimut -S

Galinpepimut-S (GPS) is an innovative and potentially first in class heteroclitic immunotherapy targeting Wilms Tumor 1 (WT1) which is ranked as the #1 cancer antigen by the National Cancer Institute. GPS consists of a mixture of four peptide fragments derived from the WT1 whole-length protein, two of which are artificially mutated by design utilizing the heteroclitic technology principle, aiming at optimal immunogenicity and mitigation of immune tolerance by the vaccinated host. GPS targets 25 carefully selected and validated WT1 antigenic epitopes and is applicable across the majority of HLA types on a global scale. GPS has an off-the-shelf lyophilized formulation and is administered subcutaneously to patients. GPS is optimally positioned either as a maintenance monotherapy in various clinical settings where the residual disease burden after prior debulking is very low, such as complete remission status in AML, or in combination with other therapeutic agents, most notably immune checkpoint inhibitors. In clinical trials, GPS has shown, both as monotherapy and in combination with checkpoint inhibitors, high rates of induction of immunogenicity and the abiitiy to delay disease relapse with an overall low incidence of adverse events, mainly low grade local inoculation reactions, and is currently being evaluated in a Phase 3 clinical trial as monotherapy for AML patients who are in second complete remission and in Phase 1 and Phase 2 studies in combination with checkpoint inhibitors. GPS was granted Orphan Drug Product Designations from the U.S. Food and Drug Administration (FDA), as well as Orphan Medicinal Product Designations from the European Medicines Agency, in AML, malignant pleural mesothelioma (MPM), and multiple myeloma (MM), as well as Fast Track Designation for AML, MPM, and MM from the FDA.

On December 7, 2020 Researchers from SWOG Cancer Research Network, a cancer clinical trials group funded by the National Cancer Institute (NCI), part of the National Institutes of Health, reported that have shown that isatuximab, a monoclonal antibody approved for the treatment of multiple myeloma, can effectively treat relapsed refractory AL amyloidosis, findings to be announced at the 2020 Annual Meeting of the American Society of Hematology (ASH) (Free ASH Whitepaper) (Press release, SWOG Cancer Research Network, DEC 7, 2020, View Source [SID1234572334]).

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AL amyloidosis is a rare disease, with about 4,500 cases diagnosed each year in the United States. Like its cancerous cousin, multiple myeloma, AL amyloidosis involves plasma cells, in this case causing them to produce abnormal protein fibers that build up in tissues and organs, leading to vital organ dysfunction, failure, and death. Many drugs that work for multiple myeloma also work for people with AL amyloidosis. However, many AL amyloidosis patients see their disease return after initial treatment, creating a need for new therapy options. The SWOG team wanted to put isatuximab to the test with these relapsed refractory patients.

Emma Scott, MD, a medical director at the pharmaceutical company GSK and an adjunct associate professor in the Division of Hematology and Medical Oncology at Oregon Health & Science University (OHSU), designed the phase II trial while working full-time at OHSU. The trial is now led by Terri Parker, MD, of Yale Cancer Center, and Vaishali Sanchorawala, MD, of Boston Medical Center. The trial, S1702, enrolled 43 patients from 32 hospitals and clinics. All patients had previously been treated for AL amyloidosis, and 35 were eligible to receive the study drug. Patients received isatuximab intravenously every week for one 28-day cycle, then every other week for as many as 24 cycles. The median treatment time was about 12 months.

Researchers’ main objective was to determine patients’ hematologic response – a blood cell count that can be a good indicator of how well the treatment is working. Of the 35 patients who took isatuximab on S1702, there was an overall response rate of 77 percent. Of the 35 patients, hematological complete response was observed in one patient, very-good-partial response was found in 19 patients, and partial response was found in seven patients.

"This is encouraging news for patients who’ve already been treated for AL amyloidosis and who are looking for another, more effective treatment," Parker said. "This is the first study of isatuximab in this disease population, and if a phase III study confirms our results, we’ve opened up another treatment option for patients with this rare disease."

The SWOG team also gathered important safety information. Overall, 19 of the 35 patients stopped treatment, the most common reasons being adverse events, disease progression, sub-optimal response, and concerns related to COVID-19. The most common drug-related side effects were generally mild. They included infusion related reactions in 17 patients, or 49 percent of those taking the study drug, along with anemia and lymphopenia. Overall, researchers found a good safety profile, one similar to other monoclonal antibodies tested in AL amyloidosis.

Parker will share results of the SWOG study in an oral presentation on Dec. 7 at 1:30 p.m. PT at the 200 ASH (Free ASH Whitepaper) meeting. The ASH (Free ASH Whitepaper) abstract number is 728, and can be found here.

S1702 was supported by the National Institutes of Health through National Cancer Institute awards CA180888, CA180819, CA180820, and CA180821 and in part by Sanofi US.

Along with Parker and Sanchorawala, the SWOG team also includes Adam Rosenthal, MS, of the SWOG Statistics and Data Management Center; Heather J. Landau, MD, of Memorial Sloan Kettering Cancer Center; Erica L. Campagnaro, MD, of University of Michigan Rogel Cancer Center; Prashant Kapoor, MD, of Mayo Clinic; Natalia Neparidze, MD, of Yale University School of Medicine; Patrick Hagen, MD, of Loyola University Medical Center; Shayna Sarosiek, MD, of Boston University Medical Center; Emma C. Scott, MD, of GSK; Antje Hoering, PhD, the SWOG Statistics and Data Management Center; Brian G.M. Durie, MD, of Cedars-Sinai Medical Center; Saad Z. Usmani, MD, of Levine Cancer Institute; and Robert Z. Orlowski, MD, PhD, of The University of Texas MD Anderson Cancer Center.

On December 7, 2020 Bellicum Pharmaceuticals, Inc. (NASDAQ:BLCM), a leader in developing novel, controllable cellular immunotherapies for cancers, reported that it has been notified by the U.S. Food and Drug Administration (FDA) that a clinical hold has been placed on patient enrollment and dosing in an ongoing Phase 1/2 dose-escalation clinical trial evaluating BPX-601 in patients with previously treated metastatic pancreatic or prostate cancer (Press release, Bellicum Pharmaceuticals, DEC 7, 2020, View Source [SID1234572350]). The FDA is taking this action due to the death of a pancreatic cancer patient in the trial reported to the agency by the company. The clinical investigator and Bellicum classified the patient death as unrelated to BPX-601 and rimiducid.

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The company plans to work diligently with the FDA to address the agency’s questions and fulfill the requirements for resuming the trial. The clinical hold does not affect the company’s plans to initiate enrollment in the Phase 1/2 clinical trial of BPX-603, a dual switch GoCAR-T, in patients with HER2+ solid tumors by the end of the year.

About BPX-601

BPX-601, the company’s first GoCAR-T product candidate, incorporates iMC, Bellicum’s inducible co-activation domain. iMC (inducible MyD88/CD40) is designed to provide a powerful boost to T cell proliferation and persistence, production of immunomodulatory cytokines and enable the CAR-T to override key immune inhibitory mechanisms, including PD-1 and TGF-beta. BPX-601 is being evaluated as a treatment for pancreatic and prostate tumors expressing prostate stem cell antigen (PSCA).