On July 6, 2023 Mersana Therapeutics, Inc. (NASDAQ:MRSN), a clinical-stage biopharmaceutical company focused on discovering and developing a pipeline of antibody-drug conjugates (ADCs) targeting cancers in areas of high unmet medical need, reported that on July 3, 2023, an authorized sub-committee of the Board of Directors of Mersana granted inducement awards, consisting of stock options to purchase an aggregate of 38,775 shares of its common stock and restricted stock unit awards (RSUs) to acquire an aggregate of 82,260 shares of its common stock, to 5 new employees whose employment commenced in June 2023 (Press release, Mersana Therapeutics, JUL 6, 2023, View Source [SID1234633083]). The awards were granted pursuant to terms and conditions fixed by the Compensation Committee and as an inducement material to each new employee entering employment with Mersana in accordance with Nasdaq Listing Rule 5635(c)(4).

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The option awards have an exercise price of $3.42 per share, which is equal to the closing price of Mersana’s common stock on July 3, 2023. Each option has a 10-year term and will vest over a period of four years, with 25% of the shares vesting on the one-year anniversary of the commencement of the employee’s employment and the remainder vesting in equal quarterly installments over the following three years, subject to the applicable employee’s continued service with Mersana on each such vesting date. The options are subject to the terms and conditions of Mersana’s 2022 Inducement Stock Incentive Plan and the terms and conditions of a stock option agreement covering each grant.

The RSUs will vest in equal annual installments on the first four anniversaries of May 15, 2023, subject to the applicable employee’s continued service with Mersana on each such vesting date. The RSUs are subject to the terms and conditions of Mersana’s 2022 Inducement Stock Incentive Plan and the terms and conditions of an RSU agreement covering each grant.

On July 6, 2023 Kazia Therapeutics Limited (NASDAQ: KZIA; ASX: KZA), an oncology-focused drug development company, reported that its lead program, paxalisib, has been awarded Fast Track Designation (FTD) by the United States Food and Drug Administration (FDA) for the treatment of solid tumor brain metastases harboring PI3K pathway mutations in combination with radiation therapy (Press release, Kazia Therapeutics, JUL 6, 2023, View Source [SID1234633082]).

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The FDA’s decision to grant FTD was based on promising clinical data from an interim analysis of an ongoing Phase 1 clinical trial in which patients with brain metastases from a primary tumour are receiving paxalisib in combination with radiotherapy (NCT04192981). These clinical data were presented at the 2022 Annual Conference on CNS Clinical Trials and Brain Metastases, jointly organized by the Society for Neuro-Oncology (SNO) and the American Society for Clinical Oncology (ASCO) (Free ASCO Whitepaper), by Dr. Jonathan Yang, lead investigator in the clinical trial. All nine evaluable patients in the trial (100%) responded to the combination of paxalisib with radiotherapy. Published benchmarks suggest a typical response rate for radiotherapy alone to be around 20-40%.

Key Points

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FTD is designed to expedite development of pharmaceutical products which demonstrate the potential to address unmet medical needs in serious or life-threatening conditions.

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FTD provides Kazia with enhanced access to FDA, including opportunities for face-to-face meetings and written consultation throughout the remaining development of paxalisib. Drugs granted FTD may also be eligible for Accelerated Approval and Priority Review, which may result in faster product approval.

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Paxalisib was previously granted FTD for glioblastoma in August 2020, giving paxalisib now two largely independent opportunities to access the benefits of this designation.

"Brain metastases are rapidly emerging as a key pillar of paxalisib’s clinical development," said Dr. John Friend, Chief Executive Officer of Kazia. "We have seen a high level of interest from clinicians in the emerging data from this patient population, and it is exciting to now have that interest complemented by FDA’s award of Fast Track Designation. With important data read-outs expected in adult and childhood brain cancer during CY2023, we will be working with investigators and advisors to drive forward our research in brain metastases also."

Brain Metastases

Brain metastases are a common complication of many tumours, but are particularly common in breast cancer, lung cancer, and melanoma. Brain metastases are typically highly resistant to treatment and survival rates are generally low. More than 250,000 patients are diagnosed with brain metastases each year in the United States alone.

Radiotherapy is a common treatment modality for brain metastases. Despite some efficacy, patients typically become resistant over time, and repeat courses of radiotherapy can be associated with significant neurological toxicity.

Expansion of Paxalisib Brain Metastases Study

The Phase I study (NCT04192981)is evaluating the safety and efficacy of paxalisib in combination with whole brain radiotherapy (WBRT) in patients with brain metastases and leptomeningeal metastases from any primary tumour (cancer that has spread to the brain from elsewhere in the body). The study was designed and initiated by Dr. Jonathan Yang, when he was at Memorial Sloan Kettering Cancer Center in New York, NY.

The study was designed in two stages. The first stage aimed to recruit 12 patients and was intended to establish the maximum tolerated dose (MTD) for paxalisib in conjunction with WBRT. Subject to positive results in the first stage, the study includes a second stage to assess initial efficacy signals and establish whether further development is warranted.

The results of the first stage of the study were reported at the SNO / ASCO (Free ASCO Whitepaper) 2022 Annual Conference on CNS Trials and Brain Metastases in August 2022. The combination was reported to be generally well-tolerated, with all nine evaluable patients showing evidence of clinical response.

Recruitment of the second stage commenced in 2H CY2022. The study is now open at two additional clinical sites: Miami Cancer Institute in Miami, FL, and the Fred Hutchinson Cancer Center in Seattle, WA, where Dr. Yang is now based.

Fast Track Designation

Introduced under the FDA Modernization Act (1997), FTD may be awarded by FDA to investigational drugs which are intended to treat a serious or life-threatening condition, and which fill an unmet medical need. FTD must be requested by the sponsor company and must be accompanied by a detailed review of both preclinical and clinical data. To be awarded FTD, drugs must generally be able to show some potential advantage over existing therapies, either in terms of safety or efficacy.

The key benefits of FTD comprise enhanced access to FDA, with regular and more frequent opportunities for consultation and discussion. In addition, drugs with FTD may be eligible for Accelerated Approval, in which a new medicine is approved based on a surrogate endpoint, and Priority Review, in which the standard 12-month review process may be reduced to eight months. Drugs with FTD may also receive a ‘rolling review’ of their NDA submission, in which sections are submitted for review as they become available, potentially expediting the approval process.

Next Steps

Further data from the ongoing Phase 1 study is expected in 1Q CY2024. Kazia continues to hold discussions with clinicians and advisors regarding the potential design of a registrational study in this indication.

Paxalisib is also the subject of nine other ongoing clinical trials, including the pivotal GBM AGILE study in glioblastoma, which is expected to provide final data in 2H CY2023, and a phase II study in pediatric patients with diffuse midline gliomas, which is expected to provide initial data in 3Q CY2023.

On July 6, 2023 IngenOx Therapeutics, IngenOx Therapeutics, an Oxford-based clinical-stage biopharma company, reported that it has been granted patents for new compounds that inhibit PRMT5 (Press release, IngenOx Therapeutics, JUL 6, 2023, View Source [SID1234633081]).

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The new patents are for the composition of matter for AT101, the focus of IngenOx’s clinical PRMT5 inhibitor programme.

This is in addition to the granted patents by the US patent office (US11485731B2) granted in November 2022 by the US Patent and Trademark Office (USPTO), the Japan patent (JP7211982B2) granted in January 2023 by the Japan Patent Office (JPO), and the Singapore patent (SG11201908598) granted in May 2023 by the Intellectual Property Office of Singapore (IPOS).

The invention relates to compounds suitable for the inhibition of protein arginine methyltransferase (PRMT), in particular PRMT5. These compounds may be used as therapeutic agents for use in the treatment of/or prevention of proliferative diseases, such as cancer.

Nick La Thangue, CEO of IngenOx, and Professor of Cancer Biology at the University of Oxford commented:"We are delighted to receive these newly granted international patents. This highlights the innovation driving IngenOx’s growth and enables us to creatively differentiate ourselves in the PRMT5 field. Moving ahead, we will profile our lead PRMT5 inhibitor, AT101, in clinical studies and seek to achieve therapeutic benefits for patients suffering with clinically unmet cancers."

On July 6, 2023 G1 Therapeutics, Inc. (Nasdaq: GTHX), a commercial-stage oncology company, reported the grant of inducement stock options exercisable for 5,600 shares of G1’s common stock and 2,800 restricted stock units (RSUs) to two hired employees under the Amended and Restated G1 Therapeutics, Inc. 2021 Inducement Equity Incentive Plan (the "Amended and Restated 2021 Plan") (Press release, G1 Therapeutics, JUL 6, 2023, View Source [SID1234633080]). These equity awards were granted as an inducement material to the new employee becoming an employee of G1 in accordance with Nasdaq Listing Rule 5635(c)(4).

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The Amended and Restated 2021 Plan is used exclusively for the grant of equity awards to individuals who were not previously employees of G1 (or following a bona fide period of non-employment), as an inducement material to such individual’s entering into employment with G1, pursuant to Rule 5635(c)(4) of the Nasdaq Listing Rules.

The stock options are exercisable at a price of $2.47 per share, the closing price of G1’s common stock on July 3, 2023, the grant date. The stock options have up to a ten-year term and vest over four years, with 25% of the award vesting on the first anniversary of the employee’s employment, and as to an additional 1/48th of the shares monthly thereafter, subject to continued service through the applicable vesting dates (subject to the terms and conditions of the stock option agreement covering the grant). The RSUs have a four-year term, with 25% of the award vesting on the first anniversary of the grant date, and the remainder vesting 12.5% semi-annually over the remaining three years, subject to continued service through the applicable vesting dates (subject to the terms and conditions of the RSU agreement covering the grant). The stock options and RSUs are subject to the terms and conditions of the Amended and Restated 2021 Plan.

On July 6, 2023 EpicentRx, Inc., a clinical stage biotechnology company with two therapeutic platforms that address cancer and inflammatory diseases, reported that the United States Adopted Name (USAN) Council in consultation with the World Health Organization’s (WHO) International Nonproprietary Names (INN) Expert Committee has assigned the generic name "nibrozetone", a shortening of the chemical name, alpha-bromodinitroazetidine, for its lead drug candidate, RRx-001 (Press release, EpicentRx, JUL 6, 2023, https://www.epicentrx.com/press-release/united-states-adopted-name-usan-council-and-international-nonproprietary-names-inn-expert-committee-recognizes-new-therapeutic-class-by-granting-nibrozetone-as-new-generic-name-f/ [SID1234633079]).

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This is the first representative of a novel class of hypoxia-activated therapeutics with a chemical scaffold, a dinitroazetidine, that is commonly found only in explosives. RRx-001 is protective under normal oxygen conditions but under low oxygen conditions that are present in tumors the molecule transforms to metabolites that disrupt the tumor microenvironment. RRx-001 is under development for the treatment of small cell lung cancer (SCLC) in a Phase 3 clinical trial, and a soon-to-start late-stage trial for the protection against oral mucositis in first line head and neck cancer, an indication for which RRx-001 has received FDA Fast Track designation. RRx-001 is proprietary to EpicentRx with issued and currently pending patents that are expected to extend coverage until 2042.

"We are pleased but not surprised given its unique aerospace-derived origins and dual mechanism of action that USAN has recognized the first-in-class nature of RRx-001 with a new generic name," stated EpicentRx’s CEO Dr. Tony Reid. "This is on the critical path for bringing a new drug to market and comes at an opportune time for EpicentRx given the late-stage trials with RRx-001 in SCLC, head and neck cancer, and radioprotection."

A nonproprietary name also known as a generic name is necessary and important, according to WHO, for "clear identification, safe prescription and dispensing of medicines to patients, and for communication and exchange of information among health professionals and scientists worldwide". To prevent potentially lethal clinical mix-ups, this name must be distinctive enough to clearly differentiate it from other medications. A multisyllabic mouthful, the chemically descriptive—and distinctive— nibrozetone is unlikely to be confused with other drug names. Therefore, and henceforth, EpicentRx will use "nibrozetone" in upcoming publications, press releases, forums, conferences, and other events or activities on the way to commercialization at which time, hopefully, a more mellifluous and shorter proprietary brand name will replace it.