On July 1, 2020 Context Therapeutics LLC, a clinical-stage biopharmaceutical company dedicated to advancing medicines for hormone driven cancers, reported that results from a safety review from preclinical and two Phase 1-2 studies evaluating its drug candidate onapristone extended release (ONA-ER) for the treatment of progesterone receptor (PR) positive cancers has been published in the journal Drug Safety. ONA-ER is an investigational, potentially best-in-class oral progesterone receptor (PR) antagonist (Press release, Context Therapeutics, JUL 1, 2020, View Source [SID1234561629]). If approved, ONA-ER would be the first FDA-approved medication for PR+ cancers.

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Antiprogestins demonstrated promising activity against breast and gynecological cancers, but liver-related safety concerns limited the advancement of this therapeutic class. Onapristone was previously evaluated in Phase 2 studies for metastatic breast cancer. Due to liver enzyme elevations identified during these studies, further development was halted. Evaluation of antiprogestin pharmacology and pharmacokinetic (PK) data suggests that liver enzyme elevations might be related to off-target effects associated with serum Cmax levels. If correct, this suggests the use of pharmaceutic strategies targeting efficacious systemic dose levels, but with a diminished Cmax. One such strategy – twice-daily dosing of an extended release (ER) formulation of onapristone (ONA-ER) – was developed and clinically evaluated in two phase 1-2 studies in PR-positive malignancies. In light of renewed interest in antiprogestin therapy for treating PR-positive breast and gynecologic cancer, the publication authors assessed the hepatotoxic potential of: (a) onapristone in liver-focused preclinical toxicology models, and (b) ONA-ER based on data from two phase 1-2 studies involving breast, ovarian, endometrial, and prostate cancer patients.

"These results suggest that the extended-release formulation by reducing drug exposure may be associated with a reduced risk of hepatotoxicity, and supports the continued clinical evaluation of ONA-ER for treating PR-positive cancers," said study author James H. Lewis, MD, Director of Hepatology at MedStar Georgetown University Hospital.

In the Phase 1-2 trials, ONA-ER at escalating doses of 10 mg to 50 mg twice-a-day had a favorable safety and tolerability profile at all doses. There were no treatment-related severe adverse events among patients treated with ONA-ER. No clinical trial subject receiving ONA-ER developed liver test elevations meeting Hy’s Law criteria or other clinically significant hepatic injury considered to be drug-related.

"Poor tolerability has limited the potential of antiprogestins for cancer patients," said Martin Lehr, Chief Executive Officer of Context. "We are pleased with the results from this review, which highlight the potential of ONA-ER to meet a significant unmet need for a well tolerated treatment for PR-positive cancers."

About Onapristone ER

Onapristone ER (extended release) is a potent and specific antagonist of the progesterone receptor that is orally administered. Currently, there are no approved therapies that selectively target progesterone receptor (PR) positive cancers. Preclinical and clinical data suggest that onapristone ER has anticancer activity by inhibiting progesterone receptor binding to chromatin, downregulating cancer stem cell mobilization and blocking immune evasion. Onapristone ER is currently being evaluated in patients with PR+ rare ovarian and endometrial cancers in the ongoing Phase 2 ONWARD 220 clinical trial. Additional Phase 2 clinical trials in ER+, PR+, HER2- breast cancer and PR-positive endometrial cancers will be initiated in 2020. Onapristone ER is an investigational drug that has not been approved for marketing by any regulatory authority.

On July 1, 2020 Blueprint Medicines Corporation (NASDAQ: BPMC), a precision therapy company focused on genomically defined cancers, rare diseases and cancer immunotherapy, reported the submission of a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) for pralsetinib for the treatment of patients with advanced or metastatic RET mutant medullary thyroid cancer (MTC) and RET fusion-positive thyroid cancers (Press release, Blueprint Medicines, JUL 1, 2020, View Source [SID1234561612]). Pralsetinib is an investigational, once-daily precision therapy designed to potently and selectively inhibit RET fusions and mutations, including predicted resistance mutations.

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Blueprint Medicines submitted the NDA under the Real-Time Oncology Review pilot program (RTOR program), an initiative of the FDA’s Oncology Center of Excellence. The RTOR program aims to explore a more efficient review process to ensure that safe and effective treatments are available to patients as early as possible, while maintaining and improving review quality by the FDA.

"Pralsetinib has broad potential to address the medical needs of patients with RET-altered cancers, who have not traditionally benefited from targeted therapy even though their tumors have a known disease driver," said Andy Boral, M.D., Ph.D., Chief Medical Officer at Blueprint Medicines. "There are now pending marketing applications for pralsetinib in RET-altered non-small cell lung cancer and thyroid cancers, supporting our goal to advance treatment standards for these patients. We are working closely with the FDA and aim to bring this promising treatment to patients as expeditiously as possible."

In May 2020, Blueprint Medicines announced that the U.S. and EU marketing applications for pralsetinib for the treatment of locally advanced or metastatic RET fusion-positive non-small cell lung cancer (NSCLC) were accepted by the FDA and validated by the European Medicines Agency, respectively.

About RET-Altered Solid Tumors

RET activating fusions and mutations are key disease drivers in many cancer types, including NSCLC and MTC. RET fusions are implicated in approximately 1 to 2 percent of patients with NSCLC and approximately 10 to 20 percent of patients with papillary thyroid cancer, while RET mutations are implicated in approximately 90 percent of patients with advanced MTC. In addition, oncogenic RET alterations are observed at low frequencies in colorectal, breast, pancreatic and other cancers, and RET fusions have been observed in patients with treatment-resistant EGFR-mutant NSCLC.

About Pralsetinib

Pralsetinib is an investigational, once-daily oral precision therapy specifically designed for highly potent and selective targeting of oncogenic RET alterations. Blueprint Medicines is developing pralsetinib for the treatment of patients with RET-altered NSCLC, thyroid cancer and other solid tumors. The FDA has granted Breakthrough Therapy Designation to pralsetinib for the treatment of RET fusion-positive NSCLC that has progressed following platinum-based chemotherapy, and RET mutation-positive MTC that requires systemic treatment and for which there are no acceptable alternative treatments.

Pralsetinib was designed by Blueprint Medicines’ research team, leveraging the company’s proprietary compound library. In preclinical studies, pralsetinib consistently demonstrated sub-nanomolar potency against the most common RET fusions, activating mutations and predicted resistance mutations. In addition, pralsetinib demonstrated markedly improved selectivity for RET compared to pharmacologically relevant kinases, including approximately 80-fold improved potency for RET versus VEGFR2. By suppressing primary and secondary mutants, pralsetinib has the potential to overcome and prevent the emergence of clinical resistance. Blueprint Medicines believes this approach will enable durable clinical responses across a diverse range of RET alterations, with a favorable safety profile.

Blueprint Medicines has an exclusive collaboration and license agreement with CStone Pharmaceuticals for the development and commercialization of pralsetinib and certain other drug candidates in Mainland China, Hong Kong, Macau and Taiwan. Blueprint Medicines retains development and commercial rights for pralsetinib in the rest of the world.

On July 1, 2020 MetVital, Inc., a privately held biopharmaceutical company developing small molecule modulators of altered glutamate metabolism for the treatment of diseases with significant unmet medical need and commercial potential, reported that the U.S. Food and Drug Administration (FDA) has notified MetVital that its lead drug candidate, "Anhydrous Enol-Oxaloacetate" (AEO) received Fast Track Designation for the treatment of patients with newly diagnosed glioblastoma multiforme (GBM) (Press release, MetVital, JUL 1, 2020, View Source [SID1234561630]).

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AEO, a patented molecule, is MetVital’s lead clinical development candidate for treatment of glioblastoma multiforme, a malicious type of brain cancer.

Fast Track is a process designed to facilitate the development and expedite the review of drugs to treat serious conditions which fill an unmet medical need. The purpose is to get important new drugs to the patient earlier.

"FDA’s Fast Track Designation for our lead drug candidate is another important milestone for MetVital, as it can potentially speed the development of this drug for glioblastoma patients," said Alan Cash, president and chief executive officer of MetVital, Inc. AEO is also being tested in Investigator-initiated clinical trials for the treatment of Amyotrophic Lateral Sclerosis (ALS), Alzheimer’s disease and in breast cancer survivors with cognitive complaints.

Anhydrous Enol-Oxaloacetate is a molecule that has demonstrated safety and efficacy in animal models with human glioblastoma tissue implants, in animal models of ALS, and in animal models of Alzheimer’s disease. US FDA Orphan Drug Designations for oxaloacetate have been received for gliomas, ALS, and hepatocellular carcinoma.

Glioblastoma multiforme is the most aggressive of the gliomas. It is often referred to as a grade IV astrocytoma, and is the most common type of brain cancer.

On July 1, 2020 Bolt Biotherapeutics, Inc., a clinical-stage biotechnology company developing its Immune-Stimulating Antibody Conjugate (ISAC) platform technology to harness the power of the innate immune system to treat cancer, reported the closing of an oversubscribed $93.5 million Series C financing (Press release, Bolt Biotherapeutics, JUL 1, 2020, View Source [SID1234561613]). Led by Sofinnova Investments, the Series C financing included participation from new investors RA Capital Management, Surveyor Capital (a Citadel Company), Rock Springs Capital, Samsara BioCapital and Pfizer Ventures as well as existing investors Novo Holdings, Vivo Capital, Pivotal bioVenture Partners and others.

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Bolt is pioneering a new category of immunotherapies that combine the precision of antibody targeting with the power of the innate immune system via activating myeloid cells and reprogramming the tumor microenvironment. Bolt has raised more than $170 million since its founding in 2015, and this new round of funding will support the continued clinical development of its lead ISAC, BDC-1001, which is delivered systemically as monotherapy for HER2-expressing cancers. The financing will also support the expansion of the company’s pipeline of Boltbody therapeutics. Bolt’s expertise in myeloid biology lays the foundation for its innovative work developing proprietary innate immune stimulants for use in ISACs.

"The support from this marquee group of biotech investors is a testament to what we have recently accomplished, in particular the start of our first clinical trial for BDC-1001," said Randall Schatzman, Ph.D., the company’s chief executive officer. "We have built a strong team with expertise in key drug development areas, and this financing round will enable us to drive our ongoing clinical study and pipeline development work forward expeditiously. The Bolt technology has potential to significantly improve how we treat certain cancers and promises durable responses for patients. In addition to BDC1001, we are currently on track to nominate our next clinical candidates later this year."

In conjunction with the financing, Jason Pitts Ph.D., principal at Sofinnova Investments, will join the company’s board of directors. He states, "We believe Bolt is well-positioned to execute on its vision of developing immuno-oncology therapies with the potential to generate systemic immunological memory and provide durable clinical benefit. I look forward to helping the company realize their goal of developing the ISAC platform across a range of solid tumor targets."

Bolt is developing BDC-1001 as a monotherapy for patients with HER2-expressing solid tumors. The drug candidate is an ISAC comprised of trastuzumab conjugated to a Bolt proprietary TLR7/8 agonist payload. In preclinical models, systemic administration of HER2-ISACs demonstrate localized immune activation that results in robust single agent activity, generation of host immunological memory against cancer and epitope spreading. Preclinical data, which were presented at SITC (Free SITC Whitepaper) 2019, demonstrated complete, durable regression of established tumors resistant to trastuzumab and immunological memory providing protection against tumor cells that no longer express the HER2 antigen in syngeneic mouse cancer models. This offers the potential for durable and meaningful responses for HER2-expressing cancers.

On July 1, 2020 BioLife Solutions, Inc. (NASDAQ: BLFS) ("BioLife" or the "Company"), a leading developer and supplier of a portfolio of class-defining bioproduction tools for cell and gene therapies, reported estimated preliminary revenue for the second quarter of 2020 of $9.6 million to $9.8 million, representing 43% to 46% growth over the same quarter in 2019 (Press release, BioLife Science, JUL 1, 2020, View Source;301087225.html [SID1234561631]).

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Mike Rice, BioLife’s CEO, commented, "Despite the continued impact of COVID-19 on the biotech industry and specifically, the cell and gene therapy market, we continued to drive revenue growth in the second quarter. In the first six months of 2020, we added 57 new customers and confirmed that our biopreservation media products have been embedded in 23 additional customer clinical trials."

The financial data presented for the second quarter of 2020 should be considered preliminary and could be subject to change as these preliminary results are based on management’s initial analysis of operations and are subject to further internal review and the Company’s independent auditor, BDO USA, LLP, who have not completed their review.