On December 5, 2023 Allarity Therapeutics, Inc. ("Allarity" or the "Company") (Nasdaq: ALLR), a clinical-stage pharmaceutical company developing novel oncology therapeutics together with drug-specific DRP companion diagnostics for personalized cancer care, reported encouraging initial results from its ongoing Phase 2 clinical trial evaluating the efficacy of its PARP inhibitor, stenoparib, in women with advanced ovarian cancer (AOC) (Press release, Allarity Therapeutics, DEC 5, 2023, View Source [SID1234638168]). Of the five evaluable patients included in the initial data analysis, one patient experienced a complete response and the other four demonstrated stable disease.

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Investigators prescreened women with AOC using Allarity’s DRP-Stenoparib CDx, a complex transcriptomic signature comprising 414 mRNA biomarkers indicative of response/resistance to the drug. Each woman was assigned a DRP-score, and those with scores above 50%, which suggested a higher likelihood of benefiting from treatment with stenoparib, were selected for treatment. Selected patients received stenoparib in a twice daily (BID) dosing regimen (200 mg morning, 400 mg evening) under a change in protocol, implemented earlier in the year, from prior once-daily dosing of 600 mg. Allarity implemented the protocol change to optimize the drug exposure taking into account the half-life of stenoparib in patients.

Of the 22 patients screened with the DRP-Stenoparib CDx, 17 DRP positive patients were identified. Eleven women have entered treatment, and among the five evaluable participants assessed up to the data evaluation cut-off, there were early signs of clinical benefit in all cases:

One patient experienced a complete response (CR) by scan (to be confirmed by second scan) and by decreased levels of CA125 (a biomarker of AOC).
One patient experienced stable disease with tumor shrinkage of 19%.
One patient experienced stable disease for more than 24 weeks with tumor
shrinkage of 11%.
Two patients experienced stable disease with tumor shrinkage of 8%.
All five patients had previously been treated with another PARP inhibitor. All five patients remain in treatment with stenoparib and the four that did not have complete responses are showing stable disease at this time.

"We are enthusiastic about these early, promising data since the observed clinical benefit indicates that stenoparib is active in advanced ovarian cancer patients selected with the DRP -Stenoparib CDx, even though these women had prior PARP inhibitor therapy and chemotherapy. While still early, these data suggest that BID dosing of this drug, and the use of the DRP -Stenoparib CDx for patient selection and treatment, may provide advanced ovarian cancer patients meaningful benefit. The DRP -Stenoparib CDx, if approved, may provide clinicians with an important diagnostic to guide patient treatment in this hard-to-treat patient population," said Marie Foegh, M.D., Chief Medical Officer of Allarity.

The initial data readout is from an ongoing Phase 2 open-label, single-arm trial that Allarity is conducting at multiple sites in the U.S. and Europe. The goal of the study is to evaluate the anti-tumor effect of stenoparib as monotherapy in DRP-selected patients with locally recurrent or metastatic ovarian cancer after previous PARP inhibitor and chemotherapy treatments. The primary endpoint is objective response rate (ORR). Allarity anticipates an interim data readout in Q1 2024.

The DRP-Stenoparib CDx is a transcriptomic signature comprising 414 mRNA biomarkers that are collectively predictive of tumor sensitivity or resistance to stenoparib. Using the DRP CDx to select likely responder patients while excluding likely resistant ones, Allarity aims to improve the benefit-risk ratio of stenoparib in metastatic or locally advanced ovarian cancer. The initial data from Allarity’s ongoing DRP-guided Phase 2 study of stenoparib suggests that the DRP-Stenoparib CDx may identify a subset of AOC patients previously treated with a PARP inhibitor who may benefit from treatment with stenoparib. The DRP-Stenoparib CDx is a clinical-stage companion diagnostic candidate and has not yet been approved by the U.S. FDA or the EU’s EMA.

All preliminary data are subject to change until the final study data readout. Early trial results may not be a reliable indicator of subsequent trial results based on a larger patient population.

About Stenoparib

Stenoparib is an orally-available, small molecule dual-targeted inhibitor of PARP1/2 and telomerase maintenance enzymes (Tankyrase 1 and 2). At present, tankyrases are attracting significant attention as emerging therapeutic targets for cancer, principally due to their role in the Wnt signaling pathway. Aberrant Wnt/β-catenin signaling has been implicated in the development and progression of multiple cancers, potentially giving stenoparib a unique, dual tumor inhibitory action. Stenoparib was originally developed by Eisai Co. Ltd. and was formerly known under the names E7449 and 2X-121. Allarity has the exclusive, global rights for the development and commercialization of stenoparib.

Some approved PARP inhibitors have recently been shown to be associated with less favorable survival outcomes than initially established. Allarity’s Phase 2 trial data for stenoparib to date shows that the drug has much less myelotoxicity than the FDA approved PARP inhibitors. Specifically, in 42 evaluable women in Phase 2 studies with stenoparib, anemia (21%), neutropenia (2%) and thrombocytopenia (0%) was lower than the approved PARP inhibitor niraparib with anemia 51%, neutropenia in 20% and thrombocytopenia oberved in in 52% of 463 patients. Allarity anticipates that this lower myelotoxicity may make stenoparib a better candidate for combination with other drugs. Allarity is studying the therapeutic potential of stenoparib in combination with dovitinib (a pan-targeted kinase inhibitor) in an ongoing Phase 1b trial, with an anticipated data readout near early Q2 2024. The Company believes that stenoparib may have broad therapeutic potential in combination with other anti-tumor agents.

On December 5, 2023 Checkpoint Therapeutics, Inc. ("Checkpoint") (Nasdaq: CKPT), a clinical-stage immunotherapy and targeted oncology company, reported that the U.S. Patent and Trademark Office ("USPTO") has issued a new patent (U.S. Patent No. 11,834,505) covering a method of treating various cancers, including cutaneous squamous cell carcinoma ("cSCC"), through the administration of cosibelimab (Press release, Checkpoint Therapeutics, DEC 5, 2023, View Source [SID1234638167]).

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The USPTO previously issued a composition of matter patent (U.S. Patent No. 10,590,199), specifically covering cosibelimab, or a fragment thereof. Together, these patents protect Checkpoint’s differentiated and potential best-in-class anti-PD-L1 antibody, cosibelimab, in the U.S. through at least May 2038, not including any potential patent term extension under the Hatch-Waxman Act.

Checkpoint’s Biologics License Application ("BLA") for cosibelimab is currently under review by the U.S. Food and Drug Administration ("FDA") as a potential new treatment for patients with locally advanced and metastatic cSCC, with an upcoming Prescription Drug User Fee Act ("PDUFA") goal date of January 3, 2024.

"With less than five weeks remaining before our assigned PDUFA date for cosibelimab, we look forward to cosibelimab potentially joining an approved class of immunotherapies with combined worldwide annual sales exceeding $35 billion," said James Oliviero, President and Chief Executive Officer of Checkpoint. "We believe our broad U.S. patent portfolio, expiring no earlier than May 2038, provides the potential for cosibelimab to be further developed into a market leading drug, not only in cSCC, but also in additional indications, both as a monotherapy and as the PD-L1 backbone for new combination regimens."

About Cosibelimab
Cosibelimab is a potential best-in-class, high affinity, fully-human monoclonal antibody of IgG1 subtype that directly binds to programmed death ligand-1 ("PD-L1") and blocks the PD-L1 interaction with the programmed death receptor-1 ("PD-1") and B7.1 receptors. Cosibelimab’s primary mechanism of action is based on the inhibition of the interaction between PD-L1 and its receptors PD-1 and B7.1, which removes the suppressive effects of PD-L1 on anti-tumor CD8+ T-cells to restore the cytotoxic T cell response. Cosibelimab is potentially differentiated from the currently marketed PD-1 and PD-L1 antibodies through sustained >99% target tumor occupancy to reactivate an antitumor immune response and the additional benefit of a functional Fc domain capable of inducing antibody-dependent cell-mediated cytotoxicity for potential enhanced efficacy in certain tumor types.

On December 5, 2023 Olema Pharmaceuticals, Inc. ("Olema" or "Olema Oncology," Nasdaq: OLMA), a clinical-stage biopharmaceutical company focused on the discovery, development and commercialization of targeted therapies for women’s cancers, reported interim results from an ongoing Phase 1b/2 clinical study of palazestrant (OP-1250) in combination with CDK4/6 inhibitor ribociclib, a Poster Spotlight Session on interim Phase 2 clinical data of palazestrant in combination with palbociclib, and a trials-in-progress poster for the OPERA-01 monotherapy Phase 3 pivotal trial at the San Antonio Breast Cancer Symposium (SABCS) at the Henry B. Gonzalez Convention Center in San Antonio, Texas (Press release, Olema Oncology, DEC 5, 2023, View Source [SID1234638165]). This disclosure was originally planned for December 7, 2023. However, on December 5, 2023, the 2023 San Antonio Breast Cancer Symposium (SABCS) published the posters ahead of schedule. These full data are scheduled to be presented on December 7, 2023, and copy of the posters are available now on Olema’s website under the Science section.

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"We believe the results we are presenting at SABCS demonstrate that palazestrant has key characteristics that make it a potential best-in-class endocrine therapy for ER+/HER2- breast cancer: complete antagonism of the estrogen receptor, favorable tolerability and tumor response, and attractive combinability with CDK4/6 inhibitors," said Sean P. Bohen, M.D., Ph.D., President and Chief Executive Officer of Olema Oncology. "OPERA-01, our Phase 3 monotherapy pivotal trial of palazestrant, has initiated, with multiple trial sites now activated and patient dosing started. The data we are gathering in our Phase 2 combination studies with CDK4/6 inhibitors, ribociclib and palbociclib, support the potential initiation of a pivotal first-line combination trial as early as the end of 2024, bringing us closer to achieving our goal of transforming the standard of care for women’s cancers."

Palazestrant Phase 1b/2 Study in Combination with Ribociclib: A poster titled "A Phase 1b/2 study of palazestrant (OP-1250) in combination with ribociclib in patients with estrogen receptor-positive, human epidermal growth factor receptor 2-negative, advanced and/or metastatic breast cancer" will be presented at SABCS. A more recent data cut, as of November 1, 2023, highlights the following:

•Across 19 patients who had completed at least one cycle of treatment as of the data cutoff date, the combination of up to 120 mg of palazestrant with 600 mg of ribociclib daily was well tolerated, with no safety signals or enhancement of toxicity and an overall safety profile remains consistent with the expected safety profile of ribociclib plus an endocrine therapy.
•Palazestrant did not affect ribociclib drug exposure in patients, and ribociclib had no clinically meaningful effect on palazestrant drug exposure.
•There were no dose-limiting toxicities, the maximum tolerated dose was not reached, and the majority of treatment-emergent adverse events were grade 1 or 2, with no grade 4 events observed. Neutropenia was reversible in all patients, and the timing was generally consistent with ribociclib-related neutropenia.
•Findings from this study support the continued use of palazestrant at the recommended Phase 2 dose of 120 mg in combination with 600mg of ribociclib, and enrollment in the dose-expansion portion of the study is ongoing.

Palazestrant Phase 1b/2 Study in Combination with Palbociclib: A poster titled "A Phase 1b/2 study of palazestrant (OP-1250), an oral complete estrogen receptor antagonist (CERAN) and selective ER degrader (SERD), with palbociclib in ER-positive, HER2-negative, advanced or metastatic breast cancer patients", will be presented in a Poster Spotlight Session by Prof. Arlene Chan, FRACP, MMed, Breast Cancer Research Centre-WA, Curtin University, Breast Clinical Trials Unit, Hollywood Private Hospital, Nedlands, Australia. The presentation will highlight that:

•
Across 46 patients as of the cutoff date of September 15, 2023, the combination of palazestrant (120 mg) with palbociclib (125 mg) daily was well tolerated, with an overall safety profile consistent with the expected safety profile of palbociclib plus an endocrine therapy.
•
There was no observed drug-drug interaction between palazestrant and palbociclib, and there was no induced metabolism or increase in exposure of either palbociclib or palazestrant when administered in combination. Most treatment-emergent adverse events were grade 1 or 2. Neutropenia incidence was similar to the PALOMA-3 study; it was reversible in all patients and the timing was generally consistent with the palbociclib-related neutropenia.
•
Tumor responses and prolonged disease stabilization were observed in this patient group, including in those previously exposed to CDK4/6 inhibitors, in both ESR1 mutant and ESR1 wild-type tumors. Partial responses were observed in seven patients, with two confirmed partial responses and five unconfirmed partial responses. The clinical benefit rate was 46% in all patients and 60% in patients with an ESR1 mutation at baseline. In patients naïve to prior CDK4/6 inhibitor treatment, the CBR was 71%. 53% of patients had any reduction in target lesion size.
•
Twenty-two (48%) patients remain on treatment, and efficacy data are still maturing. Findings from this study are consistent with previously reported data and support the ongoing clinical development of palazestrant in combination with CDK4/6 inhibitors for the treatment of ER+/HER2− metastatic breast cancer.

OPERA-01 Phase 3 Monotherapy Trial: Olema will present a poster titled "OPERA-01: A randomized, open-label, phase 3, study of palazestrant (OP-1250) vs standard-of-care treatment for ER+, HER2- advanced or metastatic breast cancer after endocrine and CDK4/6 inhibitor therapy", that detailed the ongoing clinical trial design, inclusion/exclusion criteria, and trial endpoints. Please find more details at www.opera-01.com or at clinicaltrials.gov (NCT06016738).

Company Investor Webcast and Conference Call

Olema will host a webcast and conference call for analysts and investors to review data presented at SABCS 2023 as well as other ongoing studies tomorrow, Wednesday, December 6, 2023, at 8:00 a.m. ET (7:00 a.m. CT). Please register for the webcast by visiting the Investors & Media section of Olema’s website at olema.com.

On December 05, 2023 IGM Biosciences, Inc. (Nasdaq: IGMS), a clinical-stage biotechnology company creating and developing engineered IgM antibodies, reported that it will focus its resources in two strategic areas: (i) treating colorectal cancer using IgM death receptor 5 (DR5) agonist antibodies, and (ii) treating autoimmune diseases using IgM T cell engager antibodies (Press release, IGM Biosciences, DEC 5, 2023, View Source [SID1234638164]). As an expansion of its autoimmune efforts, the Company also announced today that it plans to file an Investigational New Drug (IND) application to begin the clinical development of IGM-2644, its CD38 x CD3 T cell engager antibody, for the treatment of autoimmune diseases. As part of its strategic refocus, the Company is halting all hematologic oncology clinical development as well as the clinical development of its targeted cytokine product candidate. The Company will continue to focus on the development of oncology and immunology and inflammation product candidates under its collaboration with Sanofi. In conjunction with this strategic refocusing, the Company will be reducing its workforce by approximately 22 percent. As a result of these actions, IGM expects to extend its cash runway into the second quarter of 2026.

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"IGM continues to have a tremendous opportunity to transform a variety of disease areas using an entirely new class of antibody medicines," said Fred Schwarzer, Chief Executive Officer of IGM Biosciences. "Although we are very encouraged by the clinical and preclinical data that we have generated for the programs we are halting, given the difficult conditions in the capital markets for our industry, we have decided to focus our capital resources on those opportunities that we believe have the most potential to produce significant near-term value. We are very sorry that some of our dedicated and talented employees will be leaving IGM as part of this strategic refocusing, and we wish to extend our sincere thanks and assistance to them in this difficult transition."

Pipeline Update:

Aplitabart (DR5 agonist)

Clinical development of aplitabart in colorectal cancer prioritized.
Enrollment continues in randomized colorectal cancer clinical trial. The Company continues to enroll patients in a randomized clinical trial of aplitabart, a death receptor 5 agonist, plus FOLFIRI and bevacizumab in second-line metastatic colorectal cancer, with a goal of enrolling approximately 110 patients by the end of the first quarter of 2024. In addition to clinical trial sites in the United States, this trial includes multiple clinical trial sites in Asia and Europe.
Treatment at 10 mg/kg ongoing in the single arm colorectal cancer clinical trial continues. The Company also continues to treat later line colorectal cancer patients in its single arm combination clinical trial of 10 mg/kg of aplitabart and FOLFIRI. The Company expects to complete enrollment of patients in this 10 mg/kg single arm combination study in the first half of 2024.
Imvotamab (CD20 x CD3)

Clinical development of imvotamab in autoimmune diseases prioritized. The Company is prioritizing the clinical development of imvotamab, an IgM-based CD20 x CD3 bispecific T cell engaging antibody in autoimmune diseases. The Company currently has two Phase 1b clinical trials underway, one in severe systemic lupus erythematosus (SLE) and one in severe rheumatoid arthritis (RA). These clinical trials are being expanded to include multiple U.S. and international clinical trial sites. The Company also recently received clearance from the FDA of its IND application for the use of imvotamab in treating idiopathic inflammatory myopathies (myositis), and preparations are underway to move this clinical trial forward.
IGM-2644 (CD38 x CD3)

Clinical development of IGM-2644 in autoimmune diseases prioritized. The Company is prioritizing the clinical development of IGM-2644, a CD38 x CD3 T cell engager antibody, in the treatment of autoimmune diseases, and it plans to file an IND for these purposes in 2024.
As a part of this strategic refocusing, the Company will halt the following clinical development activities:

Aplitabart in acute myeloid leukemia and in combination with birinapant
IGM-2644 (CD38 x CD3) in multiple myeloma
IGM-2537 (CD123 x CD3)
IGM-7354 (IL-15 x PD-L1)

On December 5, 2023 VolitionRx Limited (NYSE AMERICAN: VNRX) ("Volition"), a multi-national epigenetics company, reported the company has closed on an aggregate of Euro 5.0 million (approximately $5.5 million) in financing from Wallonie Entreprendre S.A. ("WE") in Belgium (Press release, VolitionRX, DEC 5, 2023, View Source [SID1234638163]).

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Volition will use the proceeds from the financing for ongoing development of its Nu.Q product portfolio, including taking forward its clinical and regulatory program for Nu.Q NETs, which it believes will aid the early diagnosis of diseases such as sepsis.

Volition is currently working with leading clinicians and researchers at centers of excellence worldwide to help facilitate the effective introduction of Nu.Q NETs into clinical practice.

The Euro 5.0 million financing from WE consists of a Euro 2.5 million unsecured loan to Volition’s subsidiary, Belgian Volition SRL, and a Euro 2.5 million purchase of 3,205,431 shares of Volition’s restricted common stock at a purchase price of $0.8337 per share in a private placement transaction. The unsecured loan bears interest at a rate of approximately 8% per year and has a stated maturity date of December 31, 2028. Subject to certain conditions, the loan can be drawn down in three tranches at Belgian Volition’s election on or prior to June 30, 2025, with Euro 1.5 million available immediately, Euro 0.5 million available from June 1, 2024 and the final Euro 0.5 million available from March 1, 2025.

Gaetan Michel, Chief Operating Officer of Volition, said: "We are enormously grateful to WE for this latest financing, and for the ongoing financial assistance we have received from agencies within Wallonia to date."

Volition is developing simple, easy-to-use, cost-effective blood tests to help diagnose and monitor a range of life-altering diseases in both humans and animals. For more information about Volition’s Nu.Q technology go to: www.volition.com

The shares of restricted common stock were issued by Volition to WE in a private placement in reliance on an exemption from the registration requirements of the Securities Act of 1933, as amended (the "Securities Act"), and the rules and regulations promulgated thereunder. The shares of common stock will not be registered under the Securities Act or any state securities laws and unless so registered may not be offered or sold in the United States except pursuant to an exemption from, or in a transaction not subject to, the registration requirements of the Securities Act and applicable state securities laws. This announcement is neither an offer to sell nor a solicitation of an offer to buy any securities.