On April 12, 2021 Seneca Therapeutics, Inc. ("STI"), a clinical-stage biopharmaceutical company dedicated to the development of targeted oncolytic immunotherapeutics based on Seneca Valley Virus (SVV-001), reported the poster presentation of Seneca Therapeutics’ abstract titled "Oncolytic Seneca Valley Virus (SVV) overcomes resistance to checkpoint inhibitor therapies in neuroendocrine and melanoma murine models expressing the receptor for SVV" (Press release, Seneca Therapeutics, APR 12, 2021, View Source [SID1234577925]). Key points from the presentation:

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SVV-001 demonstrates the ability to turn cold tumors hot;
Intratumoral administration of SVV-001 in combination with a checkpoint inhibitor demonstrates up to six fold increase in anti-tumor response over SVV-001 alone or check point inhibitor therapy alone;
SVV-001 specifically targets, infects and kills TEM8 positive cancer cells. No cell killing was observed in normal cells;
RNA seq data confirm up regulation of genes known to stimulate an immune response;
A randomized Phase III clinical study comparing SVV-001 administered IT in combination with Opdivo and Yervoy compared to Opdivo and Yervoy alone in TEM8 positive neuroendocrine tumors and neuroendocrine carcinomas is planned to begin later in 2021. STI is also developing SVV-001 for intravenous use in TEM8 positive tumors as well as developing SVV-001 to deliver armed viruses to TEM8 positive tumor cells.

On April 12, 2021 Turning Point Therapeutics, Inc. (NASDAQ: TPTX), a precision oncology company developing next-generation therapies that target genetic drivers of cancer, reported initiation of its Phase 1/2 FORGE-1 study of TPX-0131, a potent inhibitor of the anaplastic lymphoma kinase (ALK) and multiple resistant mutations of ALK (Press release, Turning Point Therapeutics, APR 12, 2021, View Source [SID1234577924]).

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The investigational new drug (IND) application for TPX-0131 is Turning Point’s third IND to be cleared by the FDA in less than 2 years, and FORGE-1 is the company’s fourth clinical study to initiate during the same period of time.

The study was initiated in Australia, with U.S. site activations now planned.

"With a lack of available therapies to address a broad spectrum of ALK resistant mutations, we are encouraged by the preclinical potency for TPX-0131, particularly against the G1202R solvent front mutation which is reported to occur in more than 40% of biopsies with resistance mutations," said Ben Solomon, M.D., principal investigator for the FORGE-1 study, a medical oncologist and group leader of the Molecular Therapeutics and Biomarkers Laboratory at the Peter MacCallum Cancer Centre in Melbourne, Australia. "In addition, TPX-0131 has been shown preclinically to penetrate the central nervous system, which is important in the treatment of patients with ALK-positive non-small cell lung cancer as the disease often progresses in the brain."

ALK alterations are estimated to be responsible for 3% to 5% of non-small cell lung cancer (NSCLC) cases annually in the U.S. and EU5 countries. In preclinical studies, TPX-0131 potently inhibits wildtype ALK and is more potent in comparison to approved ALK inhibitors against many clinically observed resistance mutations, including the G1202R solvent front mutation, L1196M gatekeeper mutation, and multiple compound mutations. In addition, TPX-0131 has shown brain tissue penetration after repeat oral dosing.

"Our clinical study of TPX-0131 will begin with a Phase 1 dose finding portion in patients previously treated with up to 2 prior ALK tyrosine kinase inhibitors, a population we believe is underserved today by available therapies that are less potent against known resistant mutations of ALK," said Mohammad Hirmand, M.D., chief medical officer of Turning Point Therapeutics.

The Phase 1 dose finding portion of the FORGE-1 study will enroll patients with locally advanced or metastatic TKI-pretreated ALK-positive NSCLC. Patients with up to 2 prior ALK TKIs and 1 prior platinum-based chemotherapy will be enrolled. The study endpoints include safety and tolerability, determination of the maximum tolerated dose and/or the recommended Phase 2 dose, and objective response rate by RECIST 1.1.

On April 12, 2021 Kintara Therapeutics, Inc. (Nasdaq: KTRA) ("Kintara" or the "Company"), a biopharmaceutical company developing novel cancer therapies for patients who are failing, or resistant to, current treatment regimens, reported interim data results from two Phase 2 clinical trials evaluating VAL-083, the Company’s lead compound, for the treatment of glioblastoma multiforme (GBM) (Press release, Kintara Therapeutics, APR 12, 2021, View Source [SID1234577922]). The data were presented in two posters at the 2021 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting, which is taking place virtually from April 10-15, 2021.

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Poster CT238 provides an update from two patient groups receiving VAL-083 in an open-label, Phase 2 study in recurrent and adjuvant unmethylated GBM settings being conducted at the MD Anderson Cancer Center in Houston, Texas. The second poster, CT172, updates the open-label, Phase 2 study of VAL-083 as a first-line treatment in newly-diagnosed, unmethylated GBM patients being conducted at Sun Yat-sen University Cancer Center in China.

"These interim data updates at the AACR (Free AACR Whitepaper) Annual Meeting continue to demonstrate VAL-083’s potential as a game-changing treatment option for GBM patients," commented Saiid Zarrabian, Kintara’s Chief Executive Officer. "Furthermore, it’s important to note that both trials have provided valuable insights as we prepared to initiate the VAL-083 arm of the Global Coalition for Adaptive Research GBM AGILE registrational study which commenced patient enrollment in February 2021."

Poster CT238: "Phase 2 study of dianhydrogalactitol (VAL-083) in patients with MGMT-unmethylated, bevacizumab-naïve glioblastoma in the adjuvant or recurrent setting"

In newly-diagnosed patients receiving VAL-083 as adjuvant therapy following treatment with radiation and temozolomide (TMZ), for the 33 efficacy evaluable patients (of a planned 36 patients) as of the data cut-off of March 12, 2021, median progression-free survival (PFS) is currently 10.0 months (95% confidence interval: CI 8.2-10.8). While not a head-to-head study, this PFS data compares favorably to historical TMZ control of 5.3 months* and 6.9 months**, respectively.

For patients in the fully enrolled recurrent group receiving second-line therapy with VAL-083 following first-line TMZ failure, 89 patients have been enrolled as of the data cut-off of March 12, 2021 with 35 patients (35 efficacy evaluable) initially receiving a dose of 40 mg/m2/day and 54 (48 efficacy evaluable) initially receiving the treatment dose that is being carried forward in the GBM AGILE study of 30 mg/ m2/day on days 1, 2 and 3 of a 21-day cycle. Median overall survival (mOS) for the 83 efficacy evaluable patients who have completed at least once cycle of treatment was 7.5 months (CI 6.0-9.0 months). Additionally, for the 48 efficacy evaluable patients initially receiving a dose of 30 mg/ m2/day, mOS is currently 7.9 months (CI 5.9-9.9 months). While this is not a head-to-head trial, historically lomustine, which is the most commonly used chemotherapy for these patients, has demonstrated mOS of 7.2 months***.

Consistent with prior studies, myelosuppression is the most common adverse event with VAL-083 in both the recurrent GBM and adjuvant treatment settings. In the 30 mg/m2/day starting dose cohort (the dose that is being carried forward in the GBM AGILE study) seven subjects have experienced a serious adverse event (SAE) possibly related to VAL-083 in the recurrent group and one patient has experienced a possibly drug-related SAE in the adjuvant group as of the relevant data cut-off dates.

Poster CT172: "Phase 2 clinical trial of dianhydrogalactitol (VAL-083) in patients with newly-diagnosed MGMT-unmethylated GBM"

In the open-label, Phase 2 study of VAL-083 as a first-line treatment in newly-diagnosed, unmethylated GBM patients, median PFS for the 29 patients, as of the March 11, 2021 cut-off date, is currently 9.3 months (CI 6.4-12.0 months). Additionally, for the 25 patients initially receiving the treatment dose that is being carried forward in the GBM AGILE study of 30 mg/m2/day on days 1, 2 and 3 of a 21-day cycle, median PFS was reported to be 8.7 months (CI 6.4-12.5 months). While not a head-to-head study, this PFS data compares favorably to historical TMZ control of 5.3 months* and 6.9 months**, respectively. Three subjects have experienced an SAE possibly related to VAL-083. Multiple treatment cycles of VAL-083 at the 30 mg/m2/day dose in combination with standard radiation treatment (2 Gy/day, 5 days/week) were shown to be generally safe and well-tolerated. This study has been fully enrolled, and all patients have completed treatment with VAL-083 and are currently in follow-up.

On April 12, 2021 XOMA Corporation (Nasdaq: XOMA) ("XOMA" or the "Company") reported the closing of its previously announced underwritten registered public offering of 1,600,000 depositary shares, each representing a 1/1000th fractional interest in a share of the Company’s 8.375% Series B Cumulative Perpetual Preferred Stock, with liquidation preference equivalent to $25.00 per depositary share (Press release, Xoma, APR 12, 2021, View Source [SID1234577921]). The offering resulted in net proceeds of approximately $38.0 million after deducting underwriting discounts and commissions, but before expenses. The Company expects to use the net proceeds of this offering to fund the segregated dividend account and the remaining net proceeds for general corporate purposes, including funding future acquisitions of milestone and royalty rights associated with drug development programs with third-party funding. The depositary shares will be listed on Nasdaq under the symbol "XOMAO" and are expected to begin trading within 30 days.

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Book-running managers for this offering were B. Riley Securities, Inc., National Securities Corporation, Ladenburg Thalmann & Co. Inc., and William Blair & Company. Co-managers were Aegis Capital Corp., Boenning & Scattergood, Inc., Incapital LLC, and Northland Capital Markets.

The depositary shares were offered under the Company’s shelf registration statement on Form S-3, which was declared effective by the U.S. Securities and Exchange Commission ("SEC"). The offering of these depositary shares was made only by means of a prospectus supplement and accompanying base prospectus, which were filed with the SEC. A copy of the prospectus and prospectus supplement relating to these securities may be obtained on the website of the SEC at View Source or from the offices of B. Riley Securities, Inc., 1300 17th Street North, Suite 1300, Arlington, Virginia 22209, or by telephone at (703) 312-9580 or by emailing [email protected].

This press release does not constitute an offer to sell or the solicitation of an offer to buy, nor shall there be any sale of the depositary shares in any state or jurisdiction in which such offer, solicitation, or sale would not be permitted.

On April 12, 2021 Oncolytics Biotech Inc. (NASDAQ: ONCY) (TSX: ONC) reported preclinical data highlighting pelareorep’s ability to synergize with multiple classes of anti-cancer agents (Press release, Oncolytics Biotech, APR 12, 2021, View Source [SID1234577920]). The data are featured in two electronic poster presentations at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2021.

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Experiments presented in the posters evaluate the mechanisms of therapeutic synergy between pelareorep and anti-cancer agents identified via a non-biased high throughput screening assay. The top results identified in the screen were the poly(ADP)-ribose polymerase 1 (PARP-1) inhibitor talazoparib and the Cyclin-dependent kinase (CDK) 4/6 inhibitor palbociclib, which are both FDA approved for the treatment of breast cancer.

"Preclinical data presented at AACR (Free AACR Whitepaper) compel the use of pelareorep to broaden the therapeutic applicability of approved anti-cancer agents," said Thomas Heineman, M.D., Ph.D., Global Head of Clinical Development and Operations at Oncolytics. "Notably, the synergistic interactions between pelareorep and both talazoparib and palbociclib were mediated through immunological effects rather than through the molecular pathways typically associated with PARP-1 and CDK 4/6 inhibition. These findings suggest that pelareorep may expand the mechanisms by which PARP-1 and CDK 4/6 inhibitors exert anti-tumor effects, which may enhance their therapeutic potential."

Key findings from the first poster titled, "Talazoparib interacts with oncolytic reovirus to enhance death-inducing signaling complex (DISC)-mediated apoptosis and immune response" include:

Pelareorep and talazoparib synergistically increase cancer cell apoptosis in vitro and in vivo
Pelareorep and talazoparib mechanistically synergize through enhancement of IFN-β signaling pathways
Combining pelareorep with talazoparib led to enhanced anti-tumor efficacy and inhibition of recurrent tumor growth in murine tumor models
The synergistic anti-cancer effects of pelareorep-talazoparib therapy correlated with an increased immune response
Key findings from the second poster titled, "Mechanisms of therapeutic synergy between pattern recognition response agonists and cdk4 inhibitors" include:
Combining pelareorep with palbociclib increased cancer cell death in vitro and reduced in vivo tumor burden compared to pelareorep or palbociclib monotherapy
Pelareorep and palbociclib mechanistically synergize through enhancement of endoplasmic reticulum (ER) stress signaling
Pelareorep-palbociclib enhanced ER stress signaling promoted cancer cell apoptosis by increasing innate immune activation and effector function
Andrew de Guttadauro, President of Oncolytics Biotech U.S. and Global Head of Business Development, commented, "Our most recent clinical and preclinical findings support pelareorep’s potential to boost the effectiveness of various immunotherapies beyond merely checkpoint inhibitors. Moreover, these findings codify pelareorep’s position as a simple and effective enabling technology to enhance the clinical effectiveness of a wide range of immunotherapeutic agents."

The electronic posters are available for on-demand viewing on the AACR (Free AACR Whitepaper) Annual Meeting 2021 e-poster website and on the Posters & Publications page of Oncolytics’ website (LINK).

About Pelareorep

Pelareorep is a non-pathogenic, proprietary isolate of the unmodified reovirus: a first-in-class intravenously delivered immuno-oncolytic virus for the treatment of solid tumors and hematological malignancies. The compound induces selective tumor lysis and promotes an inflamed tumor phenotype through innate and adaptive immune responses to treat a variety of cancers and has been demonstrated to be able to escape neutralizing antibodies found in patients.