On March 7, 2023 Ampersand Biomedicines reported the company designed to tackle a key drug development challenge: on-target, off-tissue toxicity (Press release, Ampersand Biomedicines, MAR 7, 2023, View Source [SID1234636604]). By creating drugs that only act at the diseased tissue, regardless of whether a target is expressed elsewhere, the biotech aims to provide powerful punches without the side effects.

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Today, drug developers largely rely on differences in the levels of target expression to achieve a balance between safety and efficacy. Ideally, a receptor will only be found in the target tissue, limiting safety issues to off-target toxicity. But in reality some promising targets are found at high levels in healthy tissues, meaning safety concerns can torpedo the program.

The situation has resulted in a pool of targets that have validated roles in disease pathways but are found at too high levels in healthy tissues to be viable therapeutic opportunities. Biotech builder Flagship has spent the past two years trying to find a solution for that problem.

Now, the VC fund is ready to lift the lid on its work, albeit only by a fraction, and introduce Ampersand Biomedicines to the wider world. The biotech starts life with $50 million from Flagship and a platform for making molecules that target the site of disease without affecting healthy cells and tissues.

As is typical for early-stage biotechs, full details of exactly how Ampersand will pull off that trick are yet to emerge. The approach relies on the multiomics characterization of human biology, spanning healthy and diseased states. Using the data, Ampersand aims to identify localizers that ensure the drug only acts on particular organs or cells.

The biotech says the platform is applicable to a range of modalities—including proteins, small molecules, lipid nanoparticles and nucleic acids—and therapeutic areas. Ampersand is yet to share details of its first areas of focus.

Flagship has put together the initial leadership team for the startup, with its partner Avak Kahvejian, Ph.D., taking the founding CEO role and Raffi Afeyan, Ph.D., heading up innovation and strategy.

On March 7, 2023 Kazia Therapeutics Limited (NASDAQ: KZIA; ASX: KZA), an oncology-focused drug development company, reported that it has entered into a collaboration with the Australian and New Zealand Children’s Haematology / Oncology Group (ANZCHOG) for a phase II clinical study examining paxalisib in children with advanced solid tumours, including brain tumours (Press release, Kazia Therapeutics, MAR 7, 2023, View Source [SID1234628376]).

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The study, named OPTIMISE, will combine paxalisib with chemotherapy for children with specific genetic mutations in their tumours. The study will harness expertise and insights gained from the Zero Childhood Cancer Program, which aims to match childhood cancer patients with targeted therapies suited to the unique characteristics of their tumour.

Key Points

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New collaboration is the first Australian-led clinical trial of paxalisib.

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Zero Childhood Cancer Program, led out of the Children’s Cancer Institute and the Kids Cancer Centre at Sydney Children’s Hospital, has already enrolled more than 900 children with high-risk malignancies. Patients with PI3K pathway alterations may now be eligible to receive paxalisib.

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OPTIMISE will explore paxalisib in combination with existing chemotherapy agents for the treatment of children with high-risk malignancies, including (but not confined to) brain tumours. It will first seek to establish the optimal dosing for children in combination with chemotherapy and will then determine the efficacy and safety in biomarker-defined populations.

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Up to 18 children are anticipated to be enrolled into an initial dose escalation cohort, and up to 100 patients in a dose expansion cohort.

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The study is funded by the Australian Government, through a Medical Research Future Fund (MRFF) grant, with Kazia’s contribution consisting of drug supply and in-kind support.

"We are pleased to see this very exciting new trial move forward with paxalisib as a matched targeted therapy in a biomarker-selected paediatric population," said Dr James Garner, Chief Executive Officer of Kazia. "Our commitment to childhood cancer, especially childhood brain cancer, is already substantial. The OPTIMISE study is very complementary to the ongoing PNOC022 study in DIPG, and in addition represents a promising new opportunity to explore paxalisib in a broader range of patients. This new project speaks to the substantial ongoing interest in the drug among leading clinicians and has the potential to yield important new insights into the use of paxalisib in some new areas with very substantial unmet clinical need."

Zero Childhood Cancer Program

The Zero Childhood Cancer Precision Medicine Program (ZERO) is an international effort to identify targeted therapies for childhood malignancies. One of the key insights of recent decades in cancer treatment has been the understanding that tumours are typically driven by specific genetic mutations. Instead of taking a ‘one size fits all’ approach to their treatment, ZERO aims to provide tailored individual treatment regimens for children diagnosed with cancer.

ZERO is led by the Children’s Cancer Institute and the Kid’s Cancer Centre at Sydney Children’s Hospital, Randwick in Sydney, NSW. The Institute is a leading Australian Medical Research Institute dedicated to paediatric cancer. The principal investigators of the paxalisib arm of the OPTIMISE study are Dr Marion Mateos and Professor David Ziegler, senior clinicians at the Kids Cancer Centre with extensive track records in the field.

Next Steps

OPTIMISE is expected to commence enrolment in 2H CY2023. The study will initially launch in Australia but may expand in due course to other countries.

An international phase II study of paxalisib in combination with ONC-201 for the treatment of DIPG and DMGs, sponsored by the Pacific Pediatric Neuro-Oncology Consortium (PNOC), commenced recruitment in November 2021. Initial data is anticipated in 1H CY2023.

On March 7, 2023 Sensei Biotherapeutics, Inc. (Nasdaq: SNSE), an immuno-oncology company focused on the discovery and development of next-generation therapeutics for cancer, reported that a special committee of the Board of Directors adopted a limited duration stockholder rights agreement (the "Rights Agreement") to protect stockholder interests and maximize value for all stockholders (Press release, Sensei Biotherapeutics, MAR 7, 2023, View Source [SID1234628339]).

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The Rights Agreement is intended to reduce the likelihood that any entity, person or group is able to gain control of Sensei through open market accumulation without paying all stockholders an appropriate control premium or providing the Board sufficient opportunity to make informed judgments and take actions that are in the best interests of all stockholders.

Pursuant to the Rights Agreement, Sensei will issue, by means of a dividend, one preferred share purchase right for each outstanding share of Sensei common stock to stockholders of record on the close of business on March 17, 2023. Initially, these rights will not be exercisable and will trade with, and be represented by, the shares of Sensei common stock.

The Rights Agreement will expire on March 7, 2024, or earlier, as provided in the Rights Agreement.

The Rights Agreement is similar to other rights plans adopted by publicly-held companies. Under the Rights Agreement, the rights generally become exercisable only if a person, group or persons acting in concert (each, an "acquiring person") acquires beneficial ownership of 10% (or 20% in the case of certain investors filing on Schedule 13G) or more of the outstanding shares of Sensei common stock in a transaction not approved by the Company. In that situation, each holder of a right (other than the acquiring person, whose rights will become void and will not be exercisable) will be entitled to purchase, at the then-current exercise price, additional shares of Sensei common stock at a 50% discount. In addition, if Sensei is acquired in a merger or other business combination after an unapproved party acquires more than 10% (or 20% in the case of certain investors filing on Schedule 13G) of the outstanding shares of Sensei common stock, each holder of a right would then be entitled to purchase, at the then-current exercise price, shares of the acquiring company’s stock at a 50% discount. The Board, at its option, may exchange each right (other than rights owned by the acquiring person that have become null and void) in whole or in part, at an exchange ratio of one share of Sensei common stock per outstanding right, subject to adjustment. Except as provided in the Rights Agreement, the Board is entitled to redeem the rights at $0.0001 per right.

If a person or group that beneficially owns 10% (or 20% in the case of certain investors filing on Schedule 13G) or more of the outstanding shares of Sensei common stock prior to Sensei’s announcement of its adoption of the Rights Agreement, then that person’s or group’s existing ownership percentage will be grandfathered, although, with certain exceptions, the rights will become exercisable if at any time after the announcement of the adoption of the Rights Agreement such person or group increases its ownership of Sensei common stock. Additional information regarding the Rights Agreement will be contained in a current report on Form 8-K to be filed by Sensei with the U.S. Securities and Exchange Commission.

Sensei remains committed to engaging in constructive dialogue with its stockholders, and the rights plan is not intended to prevent or interfere with any action with respect to Sensei that the Board determines to be in the best interests of the Company and its stockholders. Instead, it will position the Board to fulfill its fiduciary duties on behalf of all stockholders by ensuring that the Board has sufficient time to make informed judgments about any attempts to control or significantly influence Sensei.

Jefferies is serving as financial advisor to Sensei and Sidley Austin LLP is serving as Sensei’s legal advisor.

On March 7, 2023 SELLAS Life Sciences Group, Inc. (NASDAQ: SLS) ("SELLAS" or the "Company") reported that the previously reported results from the final analysis of a Phase 1 clinical trial of the combination of galinpepimut-S (GPS) with the anti-PD-1 antibody nivolumab (Opdivo) in patients with relapsed WT1-expressing ovarian cancers (NCT02737787) have been published in the peer-reviewed journal Cancers (Press release, Sellas Life Sciences, MAR 7, 2023, View Source [SID1234628338]).

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"A significant unmet medical need exists for patients with advanced epithelial ovarian cancer following initial surgery and chemotherapy, with over 70% experiencing recurrence after they achieve clinical remission," said Angelos Stergiou, MD, ScD h.c., President and Chief Executive Officer of SELLAS. "Standard chemotherapy regimens have limited efficacy, as evidenced by the fact that almost half of the population of patients achieving macroscopic remission with salvage regimens do experience disease relapse within a year. Clinical research is crucial in identifying novel alternative therapies, including immunotherapies. We are encouraged by the growing collection of evidence that confirms our belief in GPS’s potential to provide disease control not only for ovarian cancer, but also for other WT1-expressing tumors, especially in combination with checkpoint blockade."

The article entitled "Phase I Study of a Multivalent WT1 Peptide Vaccine (Galinpepimut-S) in Combination with Nivolumab in Patients with WT1-Expressing Ovarian Cancer in Second or Third Remission" was published February 25, 2023 in "Advances in the Treatment of Ovarian Cancer," a special issue of the journal Cancers.

Key Takeaways of Published Study Data:

Broader than expected GPS immunologic responses encompassed both T-cells and antibodies. 91% (n=11) of patients treated had definite WT1-specific T-cell responses post-therapy, while in 88% (n=8) of evaluable patients there was emergence of immunoglobulins (IgG) against both a pool of the GPS constituent WT1 peptides and full-length WT1 protein.
Cellular and humoral robust antigen-specific immune responses translated into clear clinical benefit with 70% one-year progression-free survival demonstrated in patients who received two or more treatments of GPS and nivolumab as maintenance immunotherapy after salvage chemotherapy, compared to historic rates of up to 55% in comparable patient populations in the absence of any maintenance treatment.
Data suggest that durable responses to maintenance GPS immunotherapy can be attained in patients with WT1-expressing ovarian cancer, thus delaying measurable disease relapse. This is in contrast to salvage chemotherapy alone, which typically yields short-lived responses followed by relapse and the need for subsequent lines of therapy, i.e., worse outcomes and increased cumulative toxicity burden.
These results also corroborate previously announced findings from the final analysis of data from a Phase 1/2 study (SLS17-201/MK3475-770; NCT03761914) demonstrating that the combination of GPS with the PD-1 antibody pembrolizumab (Keytruda) is seemingly able to slow down disease progression, while according a median overall survival longer than 18 months in patients with active measurable platinum-resistant ovarian cancer that has relapsed after first or subsequent lines of therapy. This study was conducted under a Clinical Trial Collaboration and Supply Agreement with Merck & Co., Inc., Rahway, N.J., USA (known as MSD outside the United States and Canada).
About Ovarian Cancer
Ovarian cancer is one of the most common gynecologic malignancies and the fifth most frequent cause of cancer death in women in the United States. Over 22,000 cases are diagnosed annually, and there are an estimated 15,500 deaths per year. The majority of patients have widespread disease at presentation. The 5-year survival for advanced-stage disease remains less than 30 percent. Combining GPS with checkpoint inhibitor antibodies, which beneficially and profoundly alter the tumor microenvironment (TME), is hypothesized to increase the proportion of patients who develop an immune response against their cancer and potentially improve their clinical outcome over checkpoint inhibitors monotherapy, without the burden of additional toxicities.

On March 7, 2023 MacroGenics, Inc. (Nasdaq: MGNX), a biopharmaceutical company focused on developing and commercializing innovative monoclonal antibody-based therapeutics for the treatment of cancer, reported that the Company will release its financial results for the fourth quarter of 2022 after the market closes on Wednesday, March 15, 2023 (Press release, MacroGenics, MAR 7, 2023, View Source [SID1234628310]). MacroGenics will host a conference call to discuss the financial results and recent corporate progress on Wednesday, March 15, 2023, at 4:30 pm ET.

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Conference Call Information

To participate via telephone, please register in advance at this link. Upon registration, all telephone participants will receive a confirmation email detailing how to join the conference call, including the dial-in number along with a unique passcode and registrant ID that can be used to access the call. The listen-only webcast of the conference call can be accessed under "Events & Presentations" in the Investor Relations section of the Company’s website at View Source A recorded replay of the webcast will be available shortly after the conclusion of the call and archived on the Company’s website for 30 days following the call.