On April 12, 2022 Osmol Therapeutics, a privately held biopharmaceutical company focused on developing a treatment to prevent chemotherapy-induced peripheral neuropathy (CIPN), reported that it has closed the first $5.2 million tranche of a $7.5 million Series A-1 financing led by Koax Investment Partners, a fund formed by the founders of Biohaven Pharmaceuticals (Press release, Osmol Therapeutics, APR 12, 2022, View Source [SID1234612082]). Osmol’s lead drug candidate, OSM-0205, is based on Dr. Barbara Ehrlich’s research in neuronal calcium sensor-1 (NCS1) and was in-licensed from Yale University. OSM-0205 is designed to prevent the off-target calcium surge caused by taxanes and potentially other chemotherapy treatments associated with peripheral nerve damage.

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"The first tranches of our Series A-1 funding announced today will allow Osmol to complete the remaining Investigational New Drug (IND) enabling studies for OSM-0205, our lead drug candidate for the treatment of chemotherapy-induced neuropathy and will allow us to file an IND later this year," said Bob Linke, President and Chief Executive Officer, Osmol Therapeutics. "The remaining capital being raised for the Series A-1 will fund our Phase 1 bioavailability trial in the first half of 2023 and support the initiation of a Phase 2 proof-of-concept clinical study in mid-2023. We believe that OSM-0205 has the potential to address the critical need for a therapy that can prevent CIPN, a condition that can be devastating for cancer patients."

There are currently no Food and Drug Administration (FDA) approved therapies for the prevention or treatment of CIPN, a debilitating condition primarily caused by the off-target toxicity of taxanes and other commonly used chemotherapy treatments.

"Osmol Therapeutics is well-positioned to be a first mover in the treatment of CIPN. We believe that patients deserve a therapy that can reduce or eliminate this debilitating condition," said Robert Berman, M.D., Executive Chairman of Osmol, and Managing Director of Koax Investment Partners. "In addition, Osmol plans to pursue a second indication, chemotherapy induced cognitive impairment, also known as ‘chemobrain.’ OSM-0205 has the potential to provide similar protection to the central nervous system as these chemotherapy treatments cross the blood brain barrier."

About OSM-0205 and CIPN

Osmol’s lead drug, OSM-0205, is based on Dr. Barbara Ehrlich’s research in neuronal calcium sensor-1 (NCS1) at Yale University and is designed to prevent the off-target calcium surge caused by taxanes and potentially other chemotherapy treatments associated with peripheral nerve damage. Data from preclinical studies conducted by Osmol show that pre-treatment with OSM-0205 prevents the pathologic damage caused by these chemotherapy agents. CIPN affects hundreds of thousands of cancer patients every year and can compromise optimal chemotherapy dosing. There are no effective treatments for CIPN, a condition which can diminish quality of life and lead to lifelong disability.

On April 12, 2022 Exai Bio, a next-generation liquid biopsy company, reported data from its scientific research program on the discovery and validation of tumor-specific, orphan non-coding RNAs (oncRNAs), and the validation of artificial intelligence (AI) profiling of oncRNAs to accurately detect cancers of diverse tissue origins (Press release, Exai Bio, APR 12, 2022, View Source [SID1234612080]). With these capabilities, Exai Bio is positioned to develop blood tests for early detection and monitoring of residual disease of many commonly seen cancers.

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Exai Bio’s technology is based on its unique, proprietary repertoire of oncRNAs, which are an abundant class of small non-coding RNA sequences that are actively secreted only by cancer cells and not normal tissues. As such, oncRNAs can provide a robust disease signal with high sensitivity, low background and, as a result, high specificity, giving the Exai Bio oncRNA platform several advantages over currently employed mutational or epigenomic analyses of circulating tumor-derived DNA.

In a poster entitled, "Discovery and validation of orphan noncoding RNA profiles across multiple cancers in TCGA and two independent cohorts," Exai Bio is presenting a new study of more than 10,000 samples (7,942 cancer and 3,021 normal samples) from three large independent cancer cohorts. As a first step, Exai Bio identified a large class of distinct oncRNAs that were significantly present in six key cancer types, using samples from The Cancer Genome Atlas (TCGA). These six cancers (breast, colorectal, gastric, kidney, liver, and lung) represent the majority of cancer mortality worldwide.

Next, the oncRNAs from this library were independently validated in two unique IndivuType cohorts, containing 2,245 and 1,252 cancer samples, respectively, and over half of oncRNAs in the library were validated in at least one of the IndivuType cohorts.

Finally, Exai Bio developed artificial intelligence (AI) algorithms in the TCGA cohort for predicting the tissue-of-origin of a cancer sample by analyzing its oncRNA profile. The algorithm was validated and had high accuracy (>91%) in each IndivuType cohort, showing that cancer tissues-of-origin are identifiable based on oncRNA profiles alone.

These results demonstrate that oncRNAs are a unique and generalizable feature of cancers that may be applied to improve the care of cancer patients. Exai Bio is focused on early cancer detection for multiple types of cancer, including the 28 cancer types explored in the TCGA cohort, for which it has identified a proprietary library of more than 250,000 novel oncRNAs. The Exai program aims to build on the current data to translate these findings into a liquid biopsy test with broad utility for early detection of cancer and monitoring of minimal residual disease.

Patrick Arensdorf, Chief Executive Officer, Exai Bio, commented, "We’re proud of the scientific rigor we are applying to the development and validation of an RNA-based liquid biopsy approach for early cancer detection. The evidence reported today demonstrates that Exai Bio’s oncRNA platform is biologically valid, clinically oriented and highly accurate in its ability to predict cancer tissue-of-origin. These results build upon our initial discoveries of tumor-specific oncRNAs in neoadjuvant breast cancer patients and validate the presence of further specific oncRNAs across multiple tumor types. We look forward to translating these findings and advancing the development of our RNA-based liquid biopsy diagnostics platform for early cancer detection and minimal disease monitoring."

Details of the AACR (Free AACR Whitepaper) 2022 poster presentation:
Title: Discovery and validation of orphan noncoding RNA profiles across multiple cancers in TCGA and two independent cohorts
Track: PO.BCS01.05 – Applications of Bioinformatics to Cancer Biology 2
Abstract/Poster: 3353
Authors: Jeffrey Wang, Helen Li, Lisa Fish, Kimberly H. Chau, Patrick Arensdorf, Hani Goodarzi, Babak Alipanahi
Presenter: Jeffrey Wang
Date & Time: April 12, 2022 (1:30 PM – 5:00 PM)
Location: Exhibit Halls, Section 27

Posters will be available on-demand on the AACR (Free AACR Whitepaper) website for attendees (www.aacr.org) beginning at 12:00 PM CDT on April 8, 2022 until July 13, 2022. Upon release at AACR (Free AACR Whitepaper), the poster will be accessible on the publications page of Exai Bio’s website.

On April 12, 2022 Kintara Therapeutics, Inc. (Nasdaq: KTRA) ("Kintara" or the "Company"), a biopharmaceutical company focused on the development of new solid tumor cancer therapies reported that it has entered into definitive agreements with institutional investors for the purchase and sale of 16,226,416 shares of the Company’s common stock (the "Shares") and warrants to purchase 16,226,416 shares of the Company’s common stock (the "Warrants") at a combined purchase price of $0.53 per Share and related Warrant in a registered direct offering priced at-the-market under Nasdaq rules for gross proceeds of approximately $8.6 million, before deducting fees and other offering expenses (Press release, Kintara Therapeutics, APR 12, 2022, View Source [SID1234612076]). The Warrants will have an exercise price of $0.41 per share, will be exercisable immediately and will expire five years from the date of issuance. The closing of the offering is expected to occur on or about April 14, 2022, subject to the satisfaction of customary closing conditions.

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A.G.P./Alliance Global Partners is acting as sole placement agent for the offering.

The Company currently intends to use the net proceeds from the offering for funding its clinical studies, working capital and other general corporate purposes, including, but not limited to, funding acquisitions or investments in businesses, products or technologies that are complementary to the Company’s businesses, products and technologies.

The securities described above are being offered by the Company pursuant to a "shelf" registration statement on Form S-3 (File No. 333-254662) filed with the Securities and Exchange Commission (SEC) on March 24, 2021 and declared effective on April 1, 2021. The offering of the securities described herein will be made only by means of a prospectus, including a prospectus supplement, forming a part of the effective registration statement. A final prospectus supplement and accompanying prospectus relating to the securities being offered will be filed with the SEC and will be available on the SEC’s website located at View Source Electronic copies of the prospectus supplement may be obtained, when available, from A.G.P./Alliance Global Partners, 590 Madison Avenue, 28th Floor, New York, NY 10022, or by telephone at (212) 624-2060, or by email at [email protected].

This press release shall not constitute an offer to sell or a solicitation of an offer to buy these securities, nor shall there be any sale of these securities in any state or other jurisdiction in which such offer, solicitation or sale would be unlawful prior to the registration or qualification under the securities laws of any such state or other jurisdiction.

On April 12, 2022 Aptevo Therapeutics Inc. (NASDAQ:APVO), a clinical-stage biotechnology company focused on developing novel immuno-oncology therapeutics based on its proprietary ADAPTIR and ADAPTIR-FLEX platform technologies, reported the presentation of preclinical data for APVO442 in a poster session at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting in New Orleans, LA (Press release, Aptevo Therapeutics, APR 12, 2022, View Source [SID1234612075]). APVO442 is a bispecific therapeutic candidate targeting prostate-specific maturation antigen (PSMA) and CD3 designed to redirect the patient’s T cell-mediated tumor-fighting responses against PSMA-expressing solid tumors (prostate cancer).

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The presentation, entitled "APVO442 is a distinct PSMA x CD3 targeted bispecific candidate designed to optimize T cell fitness and distribution to solid tumors," highlights the potential of APVO442 to treat prostate cancer indications such as metastatic castration-resistant prostate cancer with increased benefit and decreased side effects relative to other potential therapeutics in the bispecific category. Aptevo is working to identify a clinical path for APVO442 and to potentially offer improved treatment options as a monotherapy or combination therapy for patients with difficult-to-treat prostate cancers.

"APVO442 was designed to offer unique tumor fighting and safety properties with the goal of maximizing the patients’ own immune response toward tumor killing while minimizing the toxic effects that can be associated with this bispecific therapeutic category, most notably cytokine release syndrome. This is a serious and sometimes treatment-limiting side effect in a clinical setting," said Michelle Nelson, Associate Director of Immunobiology, Aptevo Therapeutics. "We are continuing preclinical studies to support an IND-enabling package, which precedes the start of human clinical studies. The Company looks forward to presenting additional APVO442 data, our first candidate developed using our innovative APDAPTIR-FLEX platform."

About APVO442

APVO442 is a bispecific antibody candidate designed to target Prostate Specific Membrane Antigen (PSMA), a tumor antigen that is highly expressed on prostate cancer cells with limited normal tissue expression, and CD3, a signaling component of the T-cell receptor complex. APVO442 contains two binding domains to PSMA to increase binding to this tumor antigen, and a single, lower affinity binding domain to CD3. The bispecific candidate is designed to induce target-specific T-cell killing of PSMA positive cancer cells while improving concentration of the drug at the tumor site. The drug candidate is built on Aptevo’s ADAPTIR-FLEX platform and leverages the unique properties of this technology to increase binding to PSMA while lowering binding to T cells in the circulation. This design has potential to increase the amount of drug concentration at the site of PSMA-positive tumors and increase anti-tumor responses by tumor-infiltrating T cells.

On April 12, 2022 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 highlights from the six poster presentations on its pipeline programs that were presented at the American Association of Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2022, taking place April 8 – April 13, 2022 at the Ernest N. Morial Convention Center in New Orleans, LA (Press release, Molecular Templates, APR 12, 2022, View Source [SID1234612074]). Copies of the posters presented at AACR (Free AACR Whitepaper) can be found in the Investors section of Molecular Templates’ website under Presentations.

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"We believe that ETBs offer novel biology that have the potential to translate into unique clinical outcomes, even against well-explored targets," said Eric Poma, Ph.D., CEO and CSO of Molecular Templates. "We are seeing differentiated pharmacodynamic effects in patients in our Phase I study with MT-6402, our PD-L1 targeting agent, from both that agent’s direct cell-kill effects and its antigen seeding ability. We believe we can leverage this unique biology across other targets such as CTLA-4, TROP-2, and TIGIT."

Poster Title: A Phase 1 Study of MT-6402, a novel Engineered Toxin Body (ETB) targeting PD-L1, in patients with PD-L1 expressing advanced solid tumors

Authors: David R. Spigel, MD; Eugene Ahn, MD, PhD; John D. Powderly, Herbert L. Duvivier, JD, MD; Drew Rasco, MD; Agnes Rethy, MD; Chris Moore, PhD; Amy Yuet, PhD; Angela Georgy, PharmD; Sandra R. Hankins; Swati Khanna, PhD; Joseph D. Dekker, MD; Brian A. Van Tine, MD
Abstract #: 7936

Poster highlights:

Twelve patients with PD-L1+ relapsed/refractory disease have been treated to date across two dose cohorts: 16 mcg/kg (n=6) and 24 mcg/kg (n=6).
Pharmacodynamic (PD) effects including monocyte and myeloid-derived suppressor cell depletion and T cell activation have been observed in the majority of patients. The extent and timing of these PD effects appear dose-related with patients in the 24 mcg/kg cohort generally showing a more rapid and profound PD effect.
One patient in the first cohort with non-small cell lung cancer (NSCLC) (osseous non-measurable disease only) that had progressed after prior checkpoint therapy (PD-1 and CTLA-4) showed qualitative reduction in tumor burden.
One dose-limiting toxicity (DLT) was observed in a single patient (24 mcg/kg). The patient experienced dermatitis that resolved rapidly with systemic steroids. The patient was rechallenged without incident at 24 mcg/kg. No other DLTs have been reported.
Poster Title: Altering tumor immunophenotypes with PD-L1 engineered toxin bodies

Authors: Swati Khanna, Elizabeth M. Kapeel, Lauren R. Byrne, Elizabeth Saputra, Steven Rivera, Lindsey Aschenbach, Lilia A. Rabia, Garrett L. Cornelison, Rachael M. Orlandella, Brigitte Brieschke, Michaela Sousares, Jay Zhao, Garrett L. Robinson, Chris B. Moore, Joseph D. Dekker
Abstract #: 3543

Poster highlights

Molecular Templates’ Antigen Seeding Technology (AST) is a unique approach that allows for specific alteration of tumor immunophenotype to match pre-existing CD8+ T-cells in a patient. This approach is currently being tested clinically with MT-6402, a PD-L1 targeted ETB that delivers an HLA-A2 antigen derived from cytomegalovirus (CMV).
Data are presented here demonstrating that MT-6402 can be altered to present antigens derived from CMV corresponding to other HLA genotypes, thereby broadening the potential patient population that could benefit from this approach.
Poster Title: A CTLA-4-targeted ETB for Treg depletion shows favorable preclinical efficacy and safety

Authors: Asis Sarkar, Rebecca Martin, Lauren R. Byrne, Kiheon Baek, James Pazar, Caleigh Howard, Swati Khanna, Lilia A. Rabia, Diana Adhikari, Michaela M. Sousares, Alvaro Aldana, Abdul G. Khan, Garrett L. Robinson, Jay Zhao, Chris B. Moore, Aimee Iberg
Abstract #: 3538

Poster highlights:

CTLA-4-targeted ETBs are designed to preferentially deplete regulatory T cells (Tregs), via a direct cell kill mechanism of action that is independent of effector cells, in the tumor microenvironment (TME) to improve efficacy and reduce the toxicity associated with CTLA-4 targeted antibodies.
In a transgenic mouse model expressing human CTLA-4 and bearing syngeneic subcutaneous tumors, CTLA-4 ETB treatment depleted Tregs in the TME.
CTLA-4 ETB candidate was well tolerated in a non-human primate toxicology study.
Overall, these preclinical data support the use of ETB technology to deplete immune suppressive regulatory T cells in the TME to allow immune reactivation to tumor.
Poster Title: Engineered Toxin Bodies (ETBs) targeting Trop2​

Authors: Garrett L. Cornelison, Adam Bartos, Brigitte Brieschke, Jessica Momb, Ileana Pedraza, Elizabeth M. Kapeel, Rebecca Martin, Channing Pletka, Adrian Gonzalez, Joseph D. Dekker, Jay Zhao, John Majercak, Garrett L. Robinson.
Abstract: #326

Poster highlights:

Trop2 targeted ETBs show in vitro target specific picomolar potency on Trop2 positive tumor cell lines.
AST enabled Trop2 targeted ETBs to retain direct cell kill potency and alter the tumor immunophenotype to allow for antigen specific T-cell recognition.
Final lead selection based on evaluation of additional targeting domains and AST antigens is underway.
Poster Title: Improving immunotoxin-based therapeutics for cancer with de-immunized Engineered Toxin Bodies

Authors: Rachael M. Orlandella, Elizabeth M. Kapeel, Swati Khanna, Brigitte Brieschke, Garrett L. Robinson, Joseph D. Dekker, and Chris B. Moore
Abstract #: 2579

Poster highlights:

Molecular Templates has developed a de-immunized form of Shiga-like Toxin A (SLTA), incorporated into next-generation ETBs currently in clinical trials, that has demonstrated a lack of innate immune activation and capillary leak syndrome (CLS) in animal models and patients.
Ex vivo assays using peripheral blood mononuclear cells (PBMCs) demonstrate that unmodified SLTA displays upregulation of CCL3, CCL4, TNFα and IL-6, indicating a similar, but not identical, pattern of cytokine release relative to the positive control, lipopolysaccharide (LPS), while the de-immunized SLTA did not activate cytokine or chemokine release.
These data help confirm the observations in animal models and patients that indicate the de-immunized SLTA scaffold lacks the ability to trigger innate immunity seen with unmodified SLTA used in first generation ETBs.
Poster Title: C-KIT/CD117 targeted ETBs for cancer therapy and HSC transplant conditioning

Authors: Caleigh Howard, Shu Wiley, Wenzhao Dong, Andrea Mendiola, Veronica Partridge, Antonio Luz, Sara LeMar, Paul Amador, Amit Kumar Chaudhary, Joseph D. Dekker, Jay Zhao, Ross Durland, Aimee Iberg
Abstract #: 335

Poster highlights:

Molecular Templates has developed CD117 targeting ETBs that may have potential uses in myeloablation or in oncology.
CD117 ETB drug conjugates with MMAF demonstrated increased cytotoxicity compared to stand-alone ETBs or inactive ETB drug conjugate controls and also highlighted the internalization augmenting capabilities of ETBs.