On July 20, 2023 EpiBiologics, a biotechnology company advancing a next-generation antibody-based protein degradation platform and pipeline for membrane and extracellular drug targets, reported that Ann Lee-Karlon, Ph.D., will join as Chief Executive Officer, President, and member of the Board of Directors (Press release, EpiBiologics, JUL 20, 2023, View Source [SID1234643976]). Dr. Lee-Karlon will focus on expanding EpiBiologics’ proprietary EpiTAC platform, establishing value-driven collaborations, and building the company’s pipeline of bispecific antibody protein degrader therapeutics.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"I had the pleasure of working with Ann at Genentech and am confident her deep experience building therapeutic pipelines and leading strategic collaborations will be invaluable as EpiBiologics progresses novel protein degrader therapeutics toward the clinic," said David Schenkein, MD, general partner at GV. "We would like to thank Rami Hannoush for his leadership as co-founder and interim CEO and look forward to an exciting next stage of growth for EpiBiologics under Ann’s leadership."

Prior to EpiBiologics, Dr. Lee-Karlon served as Chief Operating Officer of Altos Labs. She joined Altos at its initiation in 2021 and was instrumental in building the foundation for rapid growth to 500 employees across three global sites. Before Altos, Dr. Lee-Karlon spent over 18 years at Genentech, most recently as Senior Vice President. During her tenure at Genentech, she led portfolio strategy and operations and had project leadership oversight for over 80 drug development teams from research and development through FDA approval and global launch. She led major corporate partnerships and programs, including Ocrevus for multiple sclerosis and Rituxan in immunology. Dr. Lee-Karlon holds a B.S. in bioengineering from UC Berkeley, an MBA from Stanford University, and a Ph.D. in bioengineering from UC San Diego, where she was a National Science Foundation Fellow.

"EpiBiologics has developed a groundbreaking platform to target membrane and extracellular proteins, leveraging a novel atlas of tissue-specific degrader antibodies," said Dr. Lee-Karlon, CEO of EpiBiologics. "Targeted extracellular protein degradation represents a new therapeutic modality with a wide range of applications including cancer, immunology, and neurological diseases. I’m excited to work with the outstanding scientific team, advisors, and leaders to deliver new and important treatment options for patients in need."

EpiBiologics also announced that the company brought the total series A round to $73 million with the addition of $23 million from new investors Digitalis Ventures, Taiho Ventures, and existing investor Codon Capital. In March, EpiBiologics launched with its $50 million series A financing with participation from Mubadala Capital, Polaris Partners, Vivo Capital, and GV.

EpiBiologics welcomes new members to its board of directors, including Samuel Bjork, partner at Digitalis Ventures, and Seiji Miyahara, Ph.D., senior investment director at Taiho Ventures. Board member Mitchell Mutz, Ph.D., of Vivo Capital, who led the company’s efforts to close the series A extension, will continue in his role as the CFO of EpiBiologics.

"EpiBiologics has made tremendous progress with its leading-edge EpiTAC platform, which will unravel the underlying intricacies of disease biology to build precision therapeutics," said Mr. Bjork. "We are excited to work closely with Ann as the new CEO and the entire EpiBiologics team to bring the next generation of medicines to patients."

"With Ann’s strong track record in the biopharma industry, we are thrilled to join EpiBiologics’ syndicate of investors," said Dr. Miyahara. "We look forward to helping EpiBiologics continue to develop its novel bispecific antibody platform towards important treatments for a broad range of diseases."

On July 20, 2023 ADC Therapeutics reported that it plans to discontinue the Phase 2 LOTIS-9 clinical trial evaluating ZYNLONTA (loncastuximab tesirine-lpyl) and rituximab (Lonca-R) in unfit or frail patients with previously untreated diffuse large B-cell lymphoma (DLBCL) (Press release, ADC Therapeutics, JUL 20, 2023, View Source [SID1234634579]). Given the challenges of defining the addressable segment of the difficult-to-treat unfit or frail DLBCL patient population, including many patients with significant active underlying co-morbidities, the benefit-risk profile does not support continuation of the LOTIS-9 trial.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Following a meeting yesterday, the U.S. Food and Drug Administration (FDA) placed a partial clinical hold on the trial for new patient enrollment but will allow patients already on therapy who are deriving clinical benefit to remain on therapy after being reconsented. Following treatment of any reconsenting patients, the Company will conduct the necessary steps to conclude the trial and does not plan to continue studying this regimen in the unfit or frail previously untreated DLBCL patient population.

About (loncastuximab tesirine-lpyl)

The U.S. Food and Drug Administration (FDA) and the European Medicines Agency have approved ZYNLONTA (loncastuximab tesirine-lpyl) for the treatment of adult patients with relapsed or refractory (r/r) large B-cell lymphoma after two or more lines of systemic therapy, including DLBCL not otherwise specified, DLBCL arising from low-grade lymphoma and also high-grade B-cell lymphoma. The trial included a broad spectrum of heavily pre-treated patients (median three prior lines of therapy) with difficult-to-treat disease, including patients who did not respond to first-line therapy, patients refractory to all prior lines of therapy, patients with double/triple hit genetics and patients who had stem cell transplant and CAR-T therapy prior to their treatment with ZYNLONTA. This indication is approved by the FDA under accelerated approval and in the European Union under conditional approval based on overall response rate and continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial. Please see full prescribing information including important safety information about ZYNLONTA at www.ZYNLONTA.com.

On July 20, 2023, Propanc Biopharma, Inc. (the "Company") reported to have entered into a common stock purchase agreement (the "Equity Line Agreement") with an institutional investor (the "Investor") providing for an equity financing facility, pursuant to which Company has the option to request that the Investor commit to purchase up to $5,000,000 of the Company’s shares (the "Shares") of common stock, par value $0.001 per share (the "Common Stock"), over a 24-month term commencing on the date on which a registration statement filed by the Company to register the offer and resale of the Shares by the Investor (the "Registration Statement") is declared effective by the U.S. Securities and Exchange Commission (the "SEC"). Pursuant to the Equity Line Agreement, the Company has the option to exercise this right by providing a notice (a "Drawdown Notice") from the Company to the Investor setting forth the number of Shares that the Investor will purchase. The Company has agreed to use the proceeds from such issuances for the purpose of financing its research and product development activities, finished product manufacture for clinical studies, working capital requirements and general corporate purposes.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Pursuant to the Equity Line Agreement, purchases of Shares cannot occur unless and until certain conditions are met, including but not limited to, the SEC declaring the Registration Statement effective, and the maximum number of Shares that may be purchased pursuant to a Drawdown Notice cannot exceed the lesser of (i) 200% of the average daily traded value of the Common Stock during the five (5) business days immediately preceding a Drawdown Notice or (ii) $200,000; provided that in no event may a Drawdown Notice be for less than $5,000, exceed 52,500,000 Shares or cause the Investor’s ownership to exceed 4.99% of the outstanding number of shares of Common Stock immediately prior to the issuance of such Shares. The actual amount of proceeds that the Company will receive in connection with each Drawdown Notice is determined under the Equity Line Agreement by multiplying the number of Shares to be sold by the applicable purchase price per share, which is equal to 85% of the lowest traded price of the Common Stock during the 7 business days immediately following the Clearing Date, less Clearing Costs (as each such term is defined in the Equity Line Agreement).

Additionally, in connection with the Equity Line Agreement, the Company and the Investor entered into a registration rights agreement, dated July 20, 2023 (the "Registration Rights Agreement"), pursuant to which the Company agreed to register the maximum number of Shares within 45 days of the date of the Registration Rights Agreement, subject to any comments from the SEC and applicable laws, rules and regulations.

The foregoing descriptions of each of the Equity Line Agreement and the Registration Rights Agreement do not purport to be complete and are qualified in their entirety by reference to the full text of each of the Equity Line Agreement and the Registration Rights Agreement, copies of which are attached to this Current Report on Form 8-K (this "Report") as Exhibits 10.1 and 10.2.

On July 20, 2023 DURECT Corporation (Nasdaq: DRRX) ("DURECT"), a biopharmaceutical company focused on developing its epigenetic regulator program for the treatment of acute organ injury and chronic liver diseases, reported that it has entered into definitive agreements for the purchase and sale of an aggregate of 2,991,027 shares of common stock and accompanying warrants to purchase up to 2,991,027 shares of common stock in a registered direct offering (the "Offering") priced at-the-market under Nasdaq rules (Press release, DURECT, JUL 20, 2023, View Source [SID1234633357]). The shares of common stock and accompanying warrants are being sold at a combined purchase price of $5.015 per share and accompanying warrant. The warrants will have an exercise price of $4.89 per share, will be immediately exercisable and will expire five years from the date of issuance.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

The closing of the Offering is expected to occur on or about July 21, 2023, subject to customary closing conditions. The gross proceeds from the Offering are expected to be approximately $15 million, before deducting fees to the placement agents and other estimated offering expenses payable by DURECT. DURECT intends to use the net proceeds of the Offering for general corporate purposes, which may include clinical trials, research and development activities, capital expenditures, selling, general and administrative costs, facilities expansion, and to meet working capital needs.

H.C. Wainwright & Co. is acting as exclusive placement agent for the Offering.

The Offering is being made pursuant to a "shelf" registration statement on Form S-3 (File No. 333-258333) previously filed by DURECT with the Securities and Exchange Commission (the "SEC") on July 30, 2021 and declared effective by the SEC on August 16, 2021. The Offering is being made only by means of a prospectus, including a prospectus supplement, forming a part of the effective registration statement. The prospectus supplement and the accompanying prospectus relating to, and describing the terms of, the Offering will be filed with the SEC. You may get these documents for free by visiting EDGAR on the SEC website at www.sec.gov. Alternatively, copies of the prospectus supplement and accompanying prospectus can be obtained, when available, from H.C. Wainwright & Co., LLC at 430 Park Avenue, 3rd Floor, New York, NY 10022, by phone at (212) 856-5711 or e-mail at [email protected].

This press release shall not constitute an offer to sell or the 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 July 20, 2023 CatalYm reported the publication of preclinical data in Nature Communications under the title "Tumor-derived GDF-15 blocks LFA-1 dependent T cell recruitment and suppresses responses to anti-PD-1 treatment" (Press release, Catalym, JUL 20, 2023, View Source [SID1234633351]). The study reveals a central role of GDF-15 in the resistance of tumors to current immunotherapy. These findings further highlight the therapeutic significance of CatalYm’s proprietary anti-GDF-15 antibody candidate, visugromab, currently in advanced Phase 2 clinical studies.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

This foundational research, which was performed together with founder Jörg Wischhusen and collaborators, is the first to describe a mechanistic link between tumor-produced Growth Differentiation Factor-15 (GDF-15) and the LFA-1/ICAM-1 cell adhesion axis. The interaction between LFA-1/ICAM-1 is a critical step in the infiltration of T cells into the tumor microenvironment. This is essential for the extravasation of T cells from the blood vessels into the surrounding tissue. GDF-15 is primarily known for its function in feto-maternal tolerance, an immunosuppressive mechanism that protects the fetus from the mother’s immune system.

The researchers demonstrated that GDF-15 blocks LFA-1-dependent T cell recruitment into the tumor microenvironment, a prerequisite for responses to anti-PD-1/-L1 treatment but also other immunotherapeutic strategies. Conversely, the blockade of GDF-15 with antibodies like the anti-GDF-15 antibody visugromab improved T cell infiltration into tumors. Combined with a PD-1 inhibitor, it increased tumor clearance and survival with a synergistic effect. In line with these findings, serum analysis of melanoma patients showed that response to anti-PD-1 negatively correlates with GDF-15 serum levels. Therefore, GDF-15 serum levels may be a predictive biomarker for the response to anti-PD-1 therapy and overall survival in these patients. These findings further underscore the immunosuppressive role of GDF-15 in the tumor and contribute to the growing body of data supporting GDF-15-neutralizing therapy as a promising approach for hard-to-treat tumors resistant or refractory to anti-PD-1/-L1 treatment.

"Our publication is the first to demonstrate the effect of tumor-derived GDF-15 on the LFA-1/ICAM-1 axis. As this axis orchestrates cell-cell-interactions that are essential for immune-mediated tumor control, GDF-15 likely contributes to immune escape across many different tumors and therapies," said Prof. Dr. Jörg Wischhusen, Co-Founder of CatalYm and Professor at the Julius-Maximilians-University Würzburg, who is the senior author of the publication.

"Unraveling the details of the underlying biologic pathways is crucial to develop effective therapeutic approaches that can reverse tumor-mediated immunosuppression resulting in drug resistance, one of the major challenges in cancer medicine. We are committed to rapidly advancing our Phase 2 evaluation of visugromab on our mission to expand the treatment horizon for current and future immunotherapies," added Dr. Christine Schuberth-Wagner, Chief Scientific Officer at CatalYm.

The published data adds further valuable mechanistic understanding to the clinical findings from CalaYm’s GDFather (GDF-15 Antibody-mediaTed Human Effector Cell Relocation) trials with visugromab in combination with the anti-PD-1 inhibitor nivolumab in patients with advanced solid tumors. The Phase 1 (NCT04725474) study results announced in September 2022 showed an excellent safety and tolerability profile as well as significant clinical benefit in last-line tumor patients that were anti-PD-1/-L1 relapsed or refractory. Interim data from the Phase 2 (NCT04725474) trial recently presented at ASCO (Free ASCO Whitepaper) continue to demonstrate a very good safety and tolerability profile and promising early responses in major cancer indications, including non-small cell lung cancer (NSCLC), bladder cancer and hepatocellular carcinoma (HCC). Mature data readouts for efficacy and safety data of the core Phase 2a program as well as main biomarker-correlations are expected to become available by late 2023.

About the GDFATHER-2 Trials
The GDFATHER-2a trial (GDF-15 Antibody-mediaTed Human Effector Cell Relocation Phase 2) (NCT04725474) is an ongoing Phase 2a trial with several cohorts investigating the effect of visugromab (CTL-002) as monotherapy and/or in combination with a PD-1 checkpoint inhibitor in patients in various advanced-stage, relapse/refractory solid tumor types and a biomarker-selected cohort. The study can enroll > 200 patients in Simon-2-stage designs and a biomarker-evaluation directed cohort to confirm certain response rates and potential biomarker-based responder patient selection.

About Visugromab (CTL-002)
Visugromab is a humanized monoclonal antibody that neutralizes the tumor-derived Growth Differentiation Factor-15 (GDF-15). GDF-15 is an essential player in feto-maternal tolerance, a powerful mechanism that cancer cells hijack to create an immunosuppressive environment to evade destruction. By neutralizing GDF-15, visugromab reverses the immunosuppressive effects that block an efficient anti-tumor immune response in the tumor microenvironment and the draining lymph nodes. Visugromab drives an activated and differentiated immune cell infiltration into the solid tumor as well as enables priming of T cells and enhances the tumor-killing effects of T cells and NK cells. GDF-15 is currently investigated in an ongoing Phase 2 program that includes confirmatory studies in multiple solid tumor indications and the analysis of a predictive response biomarker to better identify the patients benefiting from this new class of immunotherapy.