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First Patient Dosed in Phase III ProstACT GLOBAL Study of Antibody-based Prostate Cancer Therapy Candidate, TLX591

On November 12, 2023 Telix Pharmaceuticals Limited (ASX: TLX, Telix, the Company) reported that the first patient has been dosed in the Company’s Phase III ProstACT GLOBAL study of its investigational prostate-specific membrane antigen (PSMA) targeting radio-antibody drug conjugate (rADC) therapy, TLX591 (177Lu-rosopatamab tetraxetan) (Press release, Telix Pharmaceuticals, NOV 12, 2023, View Source [SID1234637483]). TLX591 is a rADC composed of a high-specificity PSMA-targeting antibody, chelator linker, and cytotoxic lutetium (177Lu) payload. The PSMA-targeted monoclonal antibody (mAb) approach offers significantly different targeting and pharmacology to anti-PSMA small molecules.

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ProstACT GLOBAL (ClinicalTrials.gov ID: NCT04876651) is the first Phase III trial to evaluate TLX591 in adult patients with PSMA-positive metastatic castrate-resistant prostate cancer (mCRPC) administered together with Standard of Care (SoC, androgen receptor inhibition or taxanes) versus SoC alone. Integration with current real-world SoC differentiates ProstACT GLOBAL from other PSMA studies and reflects Telix’s continued innovation in prostate cancer care and commitment to patient outcomes.

To date, 242 patients have been treated across eight Phase I and II studies of TLX591, including Telix’s ProstACT SELECT study (ClinicalTrials.gov ID: NCT04786847), which confirmed the clinical validity of Telix’s optimal fractionated dosing and product safety profile. Prior published Phase II (single-arm) study data reported a 42.3 month overall survival (OS) and an acceptable safety profile when delivered under a fractionated dosing regimen administered concurrently with docetaxel chemotherapy.[1] Compared to other radioligand therapies, collective long-term follow-up of patients administered with TLX591 has not observed significant acute or delayed nephrotoxicity due to the hepatic clearance of the agent.[2]

Preliminary data from the recently completed ProstACT SELECT study[3] demonstrated high on-target PSMA tumour-binding and radiation delivery to bone, nodal, and visceral metastases while minimising uptake and toxicity concerns in kidney, salivary glands, and lacrimal glands. This differentiated biodistribution is significant when compared to small molecule diagnostic and therapeutic PSMA agents, as uptake may not be strictly limited to cancerous tissue. The SELECT results also confirm the clinical advantage of the short, simple treatment regimen of two doses administered 14 days apart, while demonstrating the longer retention, internalisation, and potential therapeutic benefits of the 177Lu-labelled PSMA-antibody targeting approach.[3]

ProstACT GLOBAL builds on the previous Phase I and II studies of TLX591, including ProstACT SELECT. It is a multinational, multicenter, prospective, randomised, controlled, open label Phase III study designed to investigate and confirm the patient benefits and risks associated with TLX591 administered together with SoC, compared to SoC alone. ProstACT GLOBAL has an overall target enrolment of ~400 patients, with the first dose successfully administered at GenesisCare’s centre at the St John of God Hospital Murdoch campus in Australia.[4]

The study is expected to expand internationally, subject to regulatory approvals, including in Europe and the United States where Telix’s investigational new drug (IND) application remains on track for filing with the US Food and Drug Administration (FDA) in Q4 2023. The planned US arm of the study will also incorporate a run-in to bridge manufacturing data to a new commercial-scale process. An interim analysis is expected after the first 120 patients.

Nat Lenzo, MD, GenesisCare Group Clinical Director Theranostics and Principal Investigator on the ProstACT GLOBAL study commented, "Recent studies, including ProstACT SELECT, have further advanced the development of this antibody-based PSMA therapy for prostate cancer patients. We have been encouraged with the safety profile, tolerability and early efficacy observed in our previous and ongoing studies, in particular for symptom control. It’s an important step forward for patients to see this investigational therapy enter a Phase III study."

Dr Colin Hayward, Group Chief Medical Officer of Telix said, "Dosing a first patient in the ProstACT GLOBAL study is a significant milestone for Telix and will help build on an already extensive data set for this product candidate. The current TLX591 experience underlines the potential benefits of an antibody-based approach in combination with real world standards of care, including physician choice of ARPI[5] or taxane. As we take this potential first-in-class rADC candidate into a large, mid-stage patient population for the first time, we would like to thank Professor Lenzo and his clinical team, as well as the patients who will contribute to the study."

Non-consolidated Financial Results for the Nine Months Ended September 30, 2023

On November 10, 2023 Oncolys BioPharma reported its Non-consolidated Financial Results for the Nine Months Ended September 30, 2023 (Press release, Oncolys BioPharma, NOV 10, 2023, View Source [SID1234639010]).

MBrace Therapeutics Raises $85 Million Series B Financing to Advance Oncology Pipeline of Innovative Antibody Drug Conjugate Candidate

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.

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.

KAZIA ANNOUNCES PUBLICATION IN MOLECULAR CANCER THERAPEUTICS HIGHLIGHTING PAXALISIB PRECLINICAL DATA IN MELANOMA

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]).

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.

Crinetics Announces November 2023 Inducement Grants Under Nasdaq Listing Rule 5635(c)(4)

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).

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.