Precision BioSciences and SpringWorks Therapeutics Dose First Patient in Expanded Phase 1/2a Clinical Trial Evaluating PBCAR269A with Nirogacestat in Patients with Relapsed/Refractory Multiple Myeloma

On June 28, 2021 Precision BioSciences, Inc. (Nasdaq: DTIL), a clinical stage biotechnology company developing allogeneic CAR T and in vivo gene correction therapies with its ARCUS genome editing platform, and SpringWorks Therapeutics, Inc. (Nasdaq: SWTX), a clinical-stage biopharmaceutical company focused on developing life-changing medicines for patients with severe rare diseases and cancer, reported that the first patient has been dosed in the combination arm of Precision’s Phase 1/2a trial evaluating PBCAR269A (Press release, Precision Biosciences, JUN 28, 2021, View Source [SID1234584395]). In the study, Precision’s investigational allogeneic BCMA-targeted CAR T cell therapy will be combined with nirogacestat, SpringWorks’ investigational gamma secretase inhibitor (GSI), in patients with relapsed/refractory (R/R) multiple myeloma.

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"We are pleased to begin dosing patients in the combination arm of our ongoing Phase 1/2a study evaluating PBCAR269A, our first-generation allogeneic CAR T candidate targeting BCMA in patients with R/R multiple myeloma. BCMA is a well-established therapeutic target for multiple myeloma and this arm of the study pairs PBCAR269A with SpringWorks’ nirogacestat, a gamma secretase inhibitor, a combination intended to offer strong mechanistic rationale for clinical benefit," said Alan List, M.D., Chief Medical Officer at Precision BioSciences. "As we look forward to sharing interim monotherapy data for PBCAR269A later this year, we are also conducting IND enabling studies to advance PBCAR269B, an immune-evading, stealth cell formulation into the clinic in 2022. We have high conviction in both our technology and BCMA as a target and we are pursuing a broad, data-driven strategy to inform our future development plans for this indication."

"We are pleased to advance this combination into the clinic so we can evaluate if nirogacestat paired with PBCAR269A offers a safe and efficacious treatment option for patients with multiple myeloma," said Saqib Islam, Chief Executive Officer of SpringWorks Therapeutics. "We have made significant progress in developing nirogacestat as a cornerstone of BCMA combination therapy across modalities and look forward to generating clinical data with all of our partners."

In September 2020, Precision and SpringWorks entered into a clinical collaboration in which Precision is sponsoring the expanded Phase 1/2a study of PBCAR269A to include nirogacestat and evaluate the safety and preliminary clinical activity of the combination therapy. Simultaneously, Precision continues to enroll patients in the highest dose cohort (Dose Level 3 at 6.0 × 106 cells/kg) in its monotherapy study with PBCAR269A.

About PBCAR269A (Clinical Trials Study Identifier: NCT04171843)

PBCAR269A is an allogeneic BCMA-targeted CAR T cell therapy candidate being evaluated for safety and preliminary clinical activity in a Phase 1/2a multicenter, nonrandomized, open-label, parallel assignment, single-dose, dose-escalation, and dose-expansion study of adults with relapsed/refractory (R/R) multiple myeloma. The starting dose of PBCAR269A is 6 x 105 CAR T cells/kg body weight with subsequent cohorts receiving escalating doses to a maximum dose of 6 x 106 CAR T cells/kg body weight.

PBCAR269A is part of a pipeline of cell-phenotype optimized allogeneic CAR T therapies derived from healthy donors and then modified via a simultaneous TCR knock-out and CAR T knock-in step with the Company’s proprietary ARCUS genome editing technology. Precision BioSciences optimizes its CAR T therapy candidates for immune cell expansion in the body by maintaining a high proportion of naïve and central memory CAR T cells.

The U.S. Food and Drug Administration (FDA) granted Fast Track Designation to PBCAR269A for the treatment of R/R multiple myeloma for which the FDA previously granted Orphan Drug Designation. The PBCAR269A clinical trial is being conducted at multiple U.S. sites.

About Nirogacestat

Nirogacestat is an investigational, oral, selective, small molecule gamma secretase inhibitor in Phase 3 clinical development for desmoid tumors, which are rare and often debilitating and disfiguring soft-tissue tumors. Gamma secretase cleaves multiple transmembrane protein complexes, including Notch, which is believed to play a role in activating pathways that contribute to desmoid tumor growth.

In addition, gamma secretase has been shown to directly cleave membrane-bound BCMA, resulting in the release of the BCMA extracellular domain, or ECD, from the cell surface. By inhibiting gamma secretase, membrane-bound BCMA can be preserved, increasing target density while reducing levels of soluble BCMA ECD, which may serve as decoy receptors for BCMA-directed therapies. Nirogacestat’s ability to enhance the activity of BCMA-directed therapies has been observed in preclinical models of multiple myeloma. SpringWorks is evaluating nirogacestat as a BCMA potentiator and has six collaborations with industry-leading BCMA developers to evaluate nirogacestat in combinations across modalities, including with an antibody-drug conjugate, two CAR T cell therapies and two bispecific antibodies. In addition, SpringWorks and Fred Hutchinson Cancer Research Center have entered into a sponsored research agreement to further characterize the ability of nirogacestat to modulate BCMA and potentiate BCMA directed therapies using a variety of preclinical and patient-derived multiple myeloma models developed by researchers at Fred Hutch.

Nirogacestat has received Orphan Drug Designation from the U.S. Food and Drug Administration (FDA) for the treatment of desmoid tumors and from the European Commission for the treatment of soft tissue sarcoma. The FDA also granted Fast Track and Breakthrough Therapy Designations for the treatment of adult patients with progressive, unresectable, recurrent or refractory desmoid tumors or deep fibromatosis.

ORIC Pharmaceuticals Announces FDA Clearance of IND Application for ORIC-533, a Highly Potent, Orally Bioavailable Small Molecule CD73 Inhibitor

On June 28, 2021 ORIC Pharmaceuticals, Inc. (Nasdaq: ORIC), a clinical stage oncology company focused on developing treatments that address mechanisms of therapeutic resistance, reported that the U.S. Food and Drug Administration (FDA) has cleared the company’s Investigational New Drug Application (IND) for ORIC-533 to proceed into a first-in-human clinical trial. ORIC-533 is a highly potent, orally bioavailable small molecule inhibitor of CD73, a key node in the adenosine pathway believed to play a central role in resistance to chemotherapy and immunotherapy-based treatment regimens (Press release, ORIC Pharmaceuticals, JUN 28, 2021, View Source [SID1234584394]).

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The FDA clearance of our IND application for ORIC-533 is a significant milestone for ORIC as we move into the clinic with a second novel, internally discovered oncology drug candidate," said Jacob Chacko, M.D., president and chief executive officer. "In preclinical studies, ORIC-533 has demonstrated higher potency within a high AMP environment compared to all CD73 and adenosine receptor inhibitors against which it was compared. Furthermore, in addition to the potential best-in-class properties of ORIC-533, we are excited about its differentiated clinical development plan that will explore its single agent activity in contrast to the combination studies that dominate the CD73 field today."

Based on a preclinical collaboration with an academic key opinion leader that generated compelling single agent activity in patient derived model systems in an undisclosed tumor type, the company plans to pursue a single agent clinical development plan in this indication. ORIC plans to initiate the Phase 1 clinical trial with ORIC-533 in the second half of 2021 to evaluate safety, PK and preliminary efficacy in cancer patients.

This is the first of three planned IND/CTA filings for 2021, with the IND filing for ORIC-944 and CTA filing for ORIC-114 expected in the second half of the year.

About ORIC-533

ORIC-533 is a highly potent, orally bioavailable small molecule inhibitor of CD73, a key node in the adenosine pathway believed to play a central role in resistance to chemotherapy and immunotherapy-based treatment regimens. ORIC-533 has demonstrated greater potency in preclinical studies compared to an antibody approach, other small molecule CD73 inhibitors and inhibitors of adenosine receptors. Preclinical data suggest ORIC-533 binds CD73 with high affinity and effectively blocks adenosine-driven immunosuppression in a high AMP environment. In preclinical studies, nanomolar concentrations of ORIC-533 efficiently rescued cytotoxic T-cell function in the presence of high AMP concentrations, reflective of AMP levels observed in tumors.

Transactions in connection with share buy-back program

On June 28, 2021 Genmab reported the initiation of a share buy-back program to mitigate dilution from warrant exercises and to honor our commitments under our Restricted Stock Units program (Press release, Genmab, JUN 28, 2021, View Source [SID1234584393]).

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The share buy-back program is expected to be completed no later than June 30, 2021 and comprises up to 200,000 shares.

The following transactions were executed under the program from June 21, 2021, to June 25, 2021:

No. of shares

Average price (DKK)

Total value (DKK)

Accumulated through last announcement

Details of each transaction are included as an appendix to this announcement.

Following these transactions, Genmab holds 292,606 shares as treasury shares, corresponding to 0.45% of the total share capital and voting rights.

The share buy-back program is undertaken in accordance with Regulation (EU) No. 596/2014 (‘MAR’) and the Commission Delegated Regulation (EU) 2016/1052, also referred to as the "Safe Harbour Regulation." Further details on the terms of the share buy-back program can be found in our company announcement no. 11 dated February 23, 2021.

Bellicum Enters License Agreement with UNC Lineberger and Mass General for Use of CaspaCIDe® Safety Switch

On June 28, 2021 Bellicum Pharmaceuticals, Inc. (NASDAQ:BLCM), a leader in developing novel, controllable cellular immunotherapies for cancers, reported it has entered into a license agreement with the University of North Carolina Lineberger Comprehensive Cancer Center (UNC Lineberger) and Massachusetts General Hospital (Mass General) covering certain intellectual property and technology rights regarding the company’s CaspaCIDe (inducible caspase-9, or iC9) safety switch and related technologies, and the use of rimiducid (Press release, Bellicum Pharmaceuticals, JUN 28, 2021, View Source [SID1234584392]). CaspaCIDe may facilitate the use of cell therapies where cytokine release syndrome and neurotoxicities have been observed, in the pursuit of novel targets with on-target/off-tumor safety concerns, and in conjunction with next generation higher potency cell therapy constructs.

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This agreement with UNC Lineberger and Mass General covers four CAR-T programs incorporating Bellicum’s technology currently in development, two of which are owned by UNC Lineberger and two of which are co-owned by both institutions. Under this agreement, upon out-license of each program to an industry partner, Bellicum will receive an upfront payment and be entitled to a percentage of certain consideration paid to the institutions by the industry partner and a single digit percent royalty on the global sales of the product. Additional details of the financial arrangements are not disclosed.

"We are thrilled by the opportunity to expand the impact of our CaspaCIDe technology to benefit patients through this agreement with leading oncology research and treatment centers of excellence," said Rick Fair, President and CEO of Bellicum Pharmaceuticals. "We believe the agreement reflects the potential value of our switch technology, which may enhance the benefit/risk profile of cell therapies. We continue to incorporate the technology into our internal programs and intend to make it more broadly available via external collaborations."

"The unique inducible caspase-9 technology covered by this agreement has the potential to improve the safety profile of cellular immunotherapies, reduce the risk of serious adverse events, and improve patient outcomes," stated Gianpietro Dotti, M.D., Co-leader, Immunology Program, UNC Lineberger. "We are pleased to incorporate Bellicum’s CaspaCIDe into four of our promising cell therapy constructs."

About CaspaCIDe

CaspaCIDe (inducible caspase-9, or iC9) is Bellicum’s chemical induction of dimerization (CID) safety switch technology designated to eliminate cells in the event of toxicity. The CaspaCIDe switch consists of the CID-binding domain coupled to the signaling domain of caspase-9, an enzyme that is part of the apoptotic pathway. Infusion of rimiducid is designed to trigger activation of this domain of caspase-9, which in turn leads to selective apoptosis of the CaspaCIDe-containing cells. In clinical studies, use of CaspaCIDe has resulted in clinical improvement in most patients as early as 24 hours after rimiducid administration. Further, because CaspaCIDe is designed to be permanently incorporated into Bellicum’s cellular therapies, the safety switch has the potential to be available for use when needed long after the initial therapy is delivered.

Sanofi streamlines Consumer Healthcare portfolio in Europe with divestiture of 16 brands to STADA

On June 28, 2021 Sanofi’s ongoing efforts to reduce the complexity of its Consumer Healthcare portfolio and accelerate its growth trajectory, reported that it has signed an agreement with STADA for the divestiture of 16 Consumer Healthcare products commercialized in Europe (Press release, Sanofi, JUN 28, 2021, View Source [SID1234584391]). The transaction with STADA ensures that these products will continue to be available to consumers.

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"As discussed during our Capital Markets Day in February, simplifying the CHC product portfolio is an important part of our strategy to focus our resources and efforts where we can bring the most value, especially to consumers. We are pleased these products will continue to be available for consumers as we focus on becoming a fully integrated standalone business" said Julie Van Ongevalle, Executive Vice-President, Sanofi and Head of Sanofi Consumer Healthcare.

The agreement covers the registrations, trademarks, and related commercial rights of 16 products across Europe.

"This acquisition further strengthens STADA as a top-five player in Europe’s consumer healthcare market, supports our growth acceleration, and is another proof point of STADA as a go-to-partner," commented STADA’s CEO, Peter Goldschmidt.

Sanofi does not anticipate any impact of this divestiture to its European-based workforce.

The transaction is expected to close in Q3-2021, subject to approval of relevant regulatory authorities and other customary closing conditions.