On November 14, 2023 MBrace Therapeutics, Inc. ("MBrace"), a privately-held biopharmaceutical company devoted to improving the lives of cancer patients through the development of antibody-drug conjugates (ADCs) against novel oncology targets, reported the completion of an $85 million Series B financing, bringing the company’s total raised to $110 million (Press release, MBrace Therapeutics, NOV 10, 2023, View Source [SID1234637632]). Funds will be used to support clinical development programs, including a first-in-human clinical trial of lead investigational ADC, MBRC-101.

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TPG led the round, investing in the company through its dedicated life sciences fund, TPG Life Sciences Innovations (TPG LSI), and its multi-sector impact strategy, The Rise Fund. The round also included new investors Avidity Partners and Cowen Healthcare Investments, as well as existing Series A investors, Venrock and Alta Partners.

Originally founded in June 2020 by Isan Chen, M.D., Renata Pasqualini, Ph.D., and Wadih Arap, M.D., Ph.D., MBrace is focused on developing lead ADC candidate, MBRC-101, and is advancing its proprietary SPARTA approach, which accelerates the development of antibody-based drugs for personalized medicine. MBrace has generated extensive preclinical data on novel drug candidates in-licensed from Rutgers, The State University of New Jersey.

"This investor syndicate shares our confidence in the potential of our novel ADC therapeutics pipeline to meaningfully impact the treatment of people with difficult-to-treat cancers," said Isan Chen, M.D., president and chief executive officer at MBrace. "This additional capital will enable us to advance our clinical programs, including entering Phase 1 study with MBRC-101 before end of year and progressing our differentiated approach to the clinical development of our additional ADC pipeline candidates. We are well poised to make significant progress in the near-term and continue on a positive growth trajectory."

MBRC-101 targets the EphA5 receptor tyrosine kinase, which is present in multiple cancers including, but not limited to, breast, non-small cell lung (NSCLC), colorectal, gastric, and pancreatic cancers. The MBrace team will present preclinical data for MBRC-101 at the San Antonio Breast Cancer Symposium on December 7, 2023.

"We are thrilled to support MBrace in improving the lives of cancer patients with significant unmet clinical need," said Carolyn Ng, Ph.D., Business Unit Partner with TPG LSI. "Powered by a team of seasoned drug developers, with support from an accomplished Board with great collective experience building successful pharmaceutical companies, MBrace is deeply committed and well positioned to realize its vision of bringing innovative first-in-class ADC therapeutics to the clinic."

The company also welcomed Christopher LeMasters, MBA, CEO of XinThera, to the MBrace Board of Directors as an independent director. XinThera is a subsidiary of Gilead Pharmaceuticals that is focused on small molecule discovery and development of oncology and immunology therapeutics. LeMasters brings decades of experience in oncology therapeutics to MBrace. In addition to LeMasters, Ng and Monal Mehta, Ph.D., of Avidity Partners will also join the Board in conjunction with the financing. These additions complement the deep expertise of existing board members Bob More of Alta Partners and Racquel Bracken of Venrock.

On November 10, 2023 Kazia Therapeutics Limited (NASDAQ: KZIA; ASX: KZA), an oncology-focused drug development company, reported the publication in Molecular Cancer Therapeutics highlighting paxalisib preclinical data stemming from the research collaboration with the Huntsman Cancer Institute at the University of Utah in Salt Lake City, UT (Press release, Kazia Therapeutics, NOV 10, 2023, View Source [SID1234637631]).

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The paper by Dr Gennie Parkman and colleagues, working in the laboratory of Professor Sheri Holmen, has shown paxalisib to be active in vitro and in vivo against preclinical models of metastatic melanoma, the most aggressive form of skin cancer. Dr Parkman’s data highlights paxalisib as a dual inhibitor of both the PI3K and MTOR pathways and cites in the manuscript that paxalisib, "may represent a promising therapeutic strategy in this disease in both the first line and MAPK inhibitor resistant setting" for BRAF-mutant cutaneous melanoma.

"This is promising data for paxalisib, which reinforces its potential for use in an area outside of our traditional brain cancer areas of focus," commented Dr John Friend, Kazia’s CEO. "We are privileged to be working with one of the world’s leading melanoma centers on this outstanding research project and hope it may lead to a new way of treating melanoma for patients without suitable therapies."

Key Points from the Publication

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Activation of the PI3K / Akt / mTOR pathway, which is the target of paxalisib, is common in melanoma and has been identified as a key resistance mechanism to some established therapies.

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In vitro: Treatment with paxalisib was observed to lead to a significant decrease in melanoma cell growth in multiple cell lines and was also observed to inhibit downstream signaling through the PI3K/AKT cascade, leading to its negative effect on melanoma cell growth.

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In vivo:

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Mice bearing tumors who were dosed with 15 mg/kg paxalisib daily; paxalisib was observed to inhibit of tumor growth and significantly extended the overall survival of these mice (p=0.0003) compared to vehicle

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In a MTG004 patient derived xenograft mouse model that is resistant to dabrafenib and trametinib (inhibitors of mutant BRAF and MEK, respectively). At day 21, the mean tumor volume in the paxalisib treated mice was observed to be significantly lower than vehicle (P = .05) or dabrafenib/trametinib treated mice (P = .01)

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The authors concluded: "Our results support the use of paxalisib as a single agent either in the first line or MAPK inhibitor resistant setting for BRAF-mutant cutaneous melanoma. In this paper, we demonstrate the beneficial use of next generation PI3K/mTOR inhibitors, notably paxalisib, to inhibit melanoma cell growth."

The paper has been published online in Molecular Cancer Therapeutics and can be accessed at the following website: View Source

Melanoma

Approximately 1 in 50 people will be diagnosed with melanoma during their lifetime. Most cases are localized to the skin and can be cured through surgical resection. However, about 20% of cases spread (metastasis) and require more complex and ongoing treatment.

Melanoma represents approximately 1% of all skin cancers, but accounts for the majority of deaths from skin cancer. For melanoma that is confined to the skin at the time of diagnosis, the five-year survival rate is 99.5%. However, for melanoma that has spread to distant sites (metastatic melanoma), the five-year survival rate falls to 32%.

Approximately 50% of patients harbor activating mutations in the BRAF gene. Such patients are typically treated with the combination of a BRAF inhibitor and a MEK inhibitor. The introduction of targeted therapies has improved the average survival of patients with BRAF-mutant metastatic melanoma from approximately 6 months to approximately 24 months. However, we believe there remains a need for additional therapeutic options to further improve survival.

Next Steps

Kazia anticipates further data from the ongoing collaboration with the Huntsman Cancer Institute in CY2024. Depending on the results, Kazia may evaluate future opportunities to launch a clinical trial of paxalisib in melanoma.

This announcement was authorized for release by Dr. John Friend, CEO.

On November 10, 2023 Crinetics Pharmaceuticals, Inc. (Nasdaq: CRNX), a clinical stage pharmaceutical company focused on the discovery, development and commercialization of novel therapeutics for rare endocrine diseases and endocrine-related tumors, reported that  the Compensation Committee of Crinetics’ Board of Directors granted non-qualified stock option awards to purchase an aggregate of 83,600 shares of its common stock to four new non-executive employees under the Crinetics Pharmaceuticals, Inc. 2021 Employment Inducement Incentive Award Plan (the "2021 Inducement Plan") (Press release, Crinetics Pharmaceuticals, NOV 10, 2023, View Source [SID1234637481]). The stock options were granted as inducements material to the employees entering into employment with Crinetics in accordance with Nasdaq Listing Rule 5635(c)(4).

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The 2021 Inducement Plan is used exclusively for the grant of equity awards to individuals who were not previously employees of Crinetics, or following a bona fide period of non-employment, as an inducement material to such individuals’ entering into employment with Crinetics, pursuant to Nasdaq Listing Rule 5635(c)(4).

The options have an exercise price of $26.93 per share, which is equal to the closing price of Crinetics’ common stock on The Nasdaq Global Select Market on November 10, 2023. The shares subject to the stock options will vest over four years, with 25% of the shares vesting on the one-year anniversary of the applicable vesting commencement date and the balance of the shares vesting in a series of 36 successive equal monthly installments thereafter, subject to each employee’s continued employment with Crinetics on such vesting dates. The options are subject to the terms and conditions of the 2021 Inducement Plan and the terms and conditions of a stock option agreement covering the grant.

On November 10, 2023 GenScript ProBio and specialized CAR-T therapy firm Curocell reported to have signed a strategic partnership MOU for the production of viral vectors necessary for the development of next generation of CAR-T therapy, marking another significant step in their ongoing collaboration (Press release, Curocell, NOV 10, 2023, View Source [SID1234637479]).

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This partnership will broaden the strategic cooperation between the two companies to encompass the entire project, including the development, production, and clinical trials of viral vectors for CAR-T therapy research and development.

Viral vectors are vehicles for drug delivery that utilize viruses to transport genetic material to the cellular interior. The demand for viral vectors is rapidly increasing due to the recent growth of the gene therapy market, which uses CAR-T therapy as its main active ingredient.

However, it has been noted that a shortage of GMP facilities producing viral vectors is causing delays in the development of gene therapies, including CAR-T therapy.

GenScript ProBio Chairman Patrick LIU, stating, "We are delighted to sign an MOU with Curocell, a local leader in CAR-T therapy, for the supply of viral vectors," and said that this partnership will "deepen our close collaboration to develop CAR-T therapy, not only in Korea but on a global scale."

Curocell CEO Gunsoo Kim said the partnership will allow the two companies to "establish a stable cooperative relationship spanning the entire process, from the developmental stage to the commercialization of CAR-T therapy." He also stated that "Curocell plans to grow as a global leader in cancer immunotherapies through its partnership with GenScript ProBio, a company expanding its global presence in the field of gene therapy."

On November 10, 2023 Imvax, Inc., a clinical-stage biotechnology company developing personalized, whole tumor-derived immunotherapies, reported two poster presentations at the 2023 Society for NeuroOncology (SNO) 28th Annual Meeting in Vancouver, British Columbia, Canada, from November 15-19, 2023 (Press release, Imvax, NOV 10, 2023, View Source [SID1234637478]).

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At the meeting, Imvax will present new data from its Phase 1b study of IGV-001 in patients with newly diagnosed glioblastoma (ndGBM), as well as information relating to the company’s ongoing randomized, multicenter, double-blind, placebo-controlled Phase 2b clinical trial of IGV-001 in patients with ndGBM.

On Friday, November 17, 2023, at 12:45 p.m. PT, Brad Elder, M.D., Director, Neurosurgical Oncology, and Associate Professor, Department of Neurological Surgery at The Ohio State University Wexner Medical Center, will present an Independent Support Session focused on the development of IGV-001 for the treatment of ndGBM.

The details of the two poster presentations are below:

Title: "Additional results from a Phase 1b study of IGV-001 in patients with newly diagnosed glioblastoma"
Number: CTIM-17
Timing: November 17, 2023, 7:30 p.m. – 9:30 p.m. PT
Presenter: Raul Perez-Olle, M.D., Ph.D.

Title: "A randomized, multicenter, double-blind, Phase 2b study of IGV-001, an autologous cell immunotherapy with antisense oligo IMV-001 targeting IGF-1R, vs placebo, in newly diagnosed glioblastoma patients"
Number: RTID-08
Timing: November 17, 2023, 7:30 p.m. – 9:30 p.m. PT
Presenter: Ian Y. Lee, M.D.