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.

On April 12, 2021 Molecular Templates, Inc. (Nasdaq: MTEM, "Molecular Templates," or "MTEM"), a clinical-stage biopharmaceutical company focused on the discovery and development of proprietary targeted biologic therapeutics, engineered toxin bodies (ETBs),reported that three posters featuring data on its pipeline programs and technology platform will be presented at the AACR (Free AACR Whitepaper) Virtual Annual Meeting I, taking place April 10-15, 2021 (Press release, Molecular Templates, APR 12, 2021, View Source [SID1234577919]).

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Title: Phase 1 Study of the Novel Immunotoxin MT-5111 in Patients with HER2+ Tumors
Authors: Zev A. Wainberg, MD; Monica M. Mita, MD; Minal A. Barve, MD; Erika P. Hamilton, MD; Andrew J. Brenner, MD, PhD; Frances Valdes, MD; Daniel Ahn, DO; Joleen Hubbard, MD; Jason Starr, DO; Christine Burnett, PhD; Joshua Pelham; Eric T. Williams, PhD; Aimee Iberg, PhD; Thomas Strack, MD; Andrés Machado Sandri, MD; Brian A. Van Tine, MD, PhD
Abstract # CT130
This poster summarizes results from a data cut in December 2020 for an ongoing Phase 1, first in human, open-label, dose escalation and expansion study of MT-5111 in subjects with HER2+ solid tumors. MT-5111 has a novel mechanism of action that may not be subject to resistance mechanisms that exist for current HER2 therapies, binds a distinct epitope on HER2 that allows for potential combination with trastuzumab-based therapies, and, at 55kDa, is significantly smaller than other HER2 antibody or ADC therapies. As of the data cut in December 2020, 16 study subjects had been treated in the 3+3 cohort escalation. The cancer types included biliary tract (n=6), breast (n=6), pancreatic (n=2), gastric (n=1), and colon (n=1). Results to date show that MT-5111 has been well tolerated at escalated doses up to Cohort 5 (4.5 µg/kg), which allowed for the progression to Cohort 6 (6.75 µg/kg). There have not been any dose limiting toxicities nor any signs of cardiotoxicity to date, and the MTD has not been reached. Pharmacokinetic data for the first 5 cohorts matched simulations based on non-human primate studies. Exposures at 4.5 µg/kg have reached approximately 5x the IC 50 of HER2-expressing cell lines.

Three patients experienced stable disease as best response per RECIST 1.1 criteria (1 pancreatic at 4.5 µg//kg, 1 breast at 2 µg//kg, 1 biliary tract at 2 µg/kg). As previously reported, one subject with metastatic breast cancer in cohort 2 (1 µg/kg) remained on treatment for 10 cycles with stable disease; although she had unmeasurable disease by RECIST criteria, she had three sub-centimeter hepatic lesions that disappeared at the end of cycle 8 before she discontinued for clinical progression/symptomatic deterioration at cycle 10. This subject had received three prior HER2 targeting regimens which initially included pertuzumab plus trastuzumab followed by trastuzumab and TDM1 as monotherapies. Dose escalation continues and no dose limiting toxicities have been observed to date at 6.75 µg/kg (Cohort 6).

The HER2+ breast cancer expansion cohort is planned to be initiated in 2Q21 at a dose of 10 μg/kg (anticipated to be a therapeutic dose level), pending adequate safety from the 10 μg/kg dose escalation cohort. Dose escalation in all HER2+ tumor types will continue (including potential cohorts beyond 10 µg/kg) to determine the recommended Phase 2 dose while the breast cancer expansion cohort collects efficacy and safety data. As doses higher than 10 μg/kg are considered to be tolerable in the dose escalation cohort, the dose will be increased in the breast cancer cohort accordingly.

Title: Preclinical Characterization of a Novel CTLA-4-Targeted ETB for Direct Treg Depletion
Authors: Khanna, Caleigh Howard, Lilia A. Rabia, Alvaro Aldana, Jay Zhao, Asis Sarkar, Eric Williams, Banmeet Anand, Betty Chang, Chris Moore, Hilario J. Ramos, Aimee Iberg — Molecular Templates Inc., Austin, TX.
Abstract # 1627
Current CTLA-4 antibodies have shown efficacy in oncology but have been limited by toxicity issues and an inability to clear regulatory T cells (Tregs) from the tumor microenvironment (TME). CTLA-4-targeted ETBs are designed to preferentially deplete Tregs in the TME to improve efficacy and reduce the toxicity associated with CTLA-4 targeted antibodies. This study explored the preclinical characterization of a lead candidate CTLA-4-targeted ETB. CTLA-4-ETB-A directly binds and specifically kills CTLA-4 positive cells in vitro and induces apoptosis of ex-vivo expanded Tregs. CTLA-4-ETB-A is designed to bind CTLA-4 in a manner unique from classic blocking antibodies and is not expected to have sustained blocking ability in vivo due to the relatively short half-life of an ETB compared to a neutralizing monoclonal antibody. The authors predict this will allow for focused Treg depletion in the TME based on target expression levels, while sparing autoreactive T cell activation in the periphery to reduce or eliminate the toxicity seen with CTLA-4 antibodies. In a transgenic mouse model expressing human CTLA-4 and bearing syngeneic subcutaneous tumors, CTLA-4 expression was highest on the Treg cells within the tumor microenvironment compared to other T cell populations and compartments. In this model, it was demonstrated that ETB treatment depletes Tregs in the TME, supporting the overall hypothesis. Peripheral CD4+ T cell proliferation was observed in response to ETB treatment. Initial tox assessment was performed in a non-human primate (NHP) model. ETB candidate A was well tolerated up to 450 μg/kg. An increase in proliferating CD4+ and CD8+ central memory T cells was observed and is a potential pharmacodynamic effect.

Title: Engineered Toxin Bodies Targeting PD-L1 to Alter Tumor Immunophenotypes and Delivery Broad Antigenic Diversity and Patient Coverage
Authors: Swati Khanna, Elizabeth Saputra, Wenzhao Dong, Lindsey Aschenbach, Lilia A. Rabia, Garrett L. Cornelison, Michaela Sousares, Jay Zhao, Lee Robinson, Betty Chang, Hilario J. Ramos, Joseph D. Dekker
Molecular Templates Inc., Austin, TX
Abstract # 1628
MT-6402 is an ETB designed to deliver a unique and dual mechanisms of action approach for directly targeting tumors that express PD-L1 on the tumor and/or the TME. Unlike current checkpoint inhibitors which only bind PD-L1 and sterically block interactions with PD-1, MT-6402 directly destroys PD-L1+ tumor and TME immune cells. MT-6402 has dual mechanisms of action that include the enzymatic destruction of ribosomes and the delivery of a viral class I antigen derived from CMV (pp65) into the targeted tumor, referred to as Antigen Seeding Technology (AST), for presentation on the target tumor cell surface to alter the tumor immunophenotype and induce a CMV specific T-cell response. MT-6402’s antigen seeding CMV pp65 payload covers the largest MHC haplotype in the US. Delivery of foreign antigens that are restricted to additional MHC haplotypes could broaden the patient population that could benefit from AST. ETBs based on MT-6402 that deliver additional antigens retain expected potency and target binding, while also activating donor CTLs with matched haplotypes. ETBs delivering antigens to a broader population are under investigation for in vivo safety, efficacy and function. The MT-6402 IND filing has been accepted by the FDA with the Phase 1 first-in-human study expected to begin dosing in 2Q21.

On April 12, 2021 Affimed N.V. (Nasdaq: AFMD), a clinical-stage immuno-oncology company committed to giving patients back their innate ability to fight cancer, reported pre-clinical data on its Innate Cell Engager (ICE) AFM24 as monotherapy and in combination with adoptively transferred NK cells at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Virtual Annual Meeting I (Press release, Affimed, APR 12, 2021, View Source [SID1234577918]).

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AFM24, an EGFR/CD16A-binding ICE, mediates antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP) and has the potential to overcome toxicity and resistance hurdles associated with current EGFR signaling inhibitors through its differentiated mechanism of action. AFM24 induces NK cell-mediated ADCC against EGFR-expressing tumor cells even in the presence of competing IgG and can induce potent cell killing in tumors independent of KRAS mutations.

In addition, data from a xenograft mouse model demonstrate that AFM24 in combination with adoptively transferred NK cells results in dose-dependent tumor regression.

"AFM24’s novel mechanism of action is independent of EGFR signaling and has the potential to change the treatment paradigm for EGFR-expressing solid tumors," said Dr. Arndt Schottelius, Affimed’s Chief Scientific Officer. "Demonstrating that AFM24, in combination with NK cells, shows tumor regression in vivo is an important pre-clinical proof of concept. Combination therapies with NK cells could broaden the potential AFM24 opportunities to treat a range of EGFR-expressing malignancies."

Affimed is currently evaluating AFM24 as monotherapy for patients with advanced EGFR-expressing solid malignancies whose disease has progressed after treatment with previous anticancer therapies. AFM24-101 is a first-in-human Phase 1/2a open-label, non-randomized, multi-center, multiple ascending dose escalation and expansion study. Additional information about the trial may be found at www.clinicaltrials.gov, using the identifier NCT04259450.

In March 2020, the U.S. Food and Drug Administration (FDA) cleared an investigational new drug application (IND) for a Phase 1/2a study investigating the combination of AFM24 with SNK-01, an autologous NK cell product of NKGen Biotech (formerly known as NKMax America), in cancer patients with EGFR-expressing tumors.

In February 2020, Affimed announced a clinical collaboration with Roche to explore the combination of AFM24 with Roche’s PD-L1 checkpoint inhibitor atezolizumab (Tecentriq).