On April 20, 2023 Rakovina Therapeutics Inc. (the "Company") (TSXV:RKV) reported the presentation of new data describing the progress of the Company’s kt-3000 drug development program at the American Association of Cancer Research (AACR) (Free AACR Whitepaper) annual meeting in Orlando, Florida (Press release, Rakovina Therapeutics, APR 20, 2023, View Source [SID1234630362]).

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 Company’s data was presented in the DNA Damage Response section at the AACR (Free AACR Whitepaper) annual meeting in a poster entitled "A novel bi-functional agent targeting PARP and HDAC in Ewing sarcoma".

Ewing sarcoma is a highly aggressive bone and soft tissue tumor affecting mainly children and young adults, with a dismal 5-year survival rate of 15-30% for metastatic disease. Previous studies have demonstrated that Ewing sarcoma cells are sensitive to FDA-approved PARP inhibitors, but clinical trials have failed to produce a durable treatment response.

Rakovina Therapeutics’ kt-3000 series is a novel class of DNA-damage response inhibitors with dual PARP HDAC inhibitor functionality.

The combination of a PARP inhibitor with an HDAC inhibitor have shown potential synergy in laboratory studies. However, the clinical treatment of patients with the combination to date has been associated with significant side effects, limiting the adoption of this therapeutic strategy.

The kt-3000 series was designed based on the hypothesis that combining both HDAC and PARP inhibition into a single molecule would provide a more viable approach to providing clinical benefit to patients, while retaining efficacy and limiting side effects.

Data presented at the meeting demonstrate that Rakovina Therapeutics’ kt-3000 prototype lead candidate exhibits higher PARP-1 vs. PARP-2 selectivity compared to the FDA-approved PARP inhibitor, olaparib. Selectivity against PARP1 is believed to correlate with an improved safety profile vs. first-generation PARP inhibitors.

The data also demonstrate that the dual functional kt-3000 prototype lead candidate is more effective against Ewing sarcoma tumor cells than either a PARP inhibitor or HDAC inhibitor alone. This is achieved despite reduced potency at HDAC compared to the FDA-approved HDAC inhibitor, vorinostat.

The kt-3000 lead candidate effectively reduced lung metastases in mice inoculated with Ewing sarcoma tumor cells. The most common site where Ewing sarcoma metastasizes, or spreads, in patients is to their lungs, which is a leading cause of morbidity and mortality.

"The kt-3000 series compounds were designed with an aim of achieving synergistic PARP+HDAC activity against treatment of resistant tumors while improving safety and tolerability of treatment," said Prof. Mads Daugaard, Rakovina Therapeutics’ president and chief scientific officer.

"We believe that this profile offers potential as a new treatment for tumors traditionally resistant to therapy, particularly in the recurrent disease setting for Ewing sarcoma and major cancers such as breast and ovarian cancer that has become resistant to treatment with FDA-approved PARP inhibitors," he added.

Select kt-3000 lead candidates are being evaluated for pharmacokinetics and safety in vivo as part of the process to select a primary lead candidate for advancement to human clinical trials.

On April 20, 2023 Autolus Therapeutics plc (Nasdaq: AUTL), a clinical-stage biopharmaceutical company developing next-generation programmed T cell therapies, reported that it will release its first quarter 2023 financial results and operational highlights before open of U.S. markets on Thursday, May 4, 2023 (Press release, Autolus, APR 20, 2023, View Source [SID1234630361]).

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!

Management will host a conference call and webcast at 8:30 am ET/1:30 pm GMT to discuss the company’s financial results and provide a general business update. Conference call participants should pre-register using this link to receive the dial-in numbers and a personal PIN, which are required to access the conference call.

A simultaneous audio webcast and replay will be accessible on the events section of Autolus’ website.

On April 20, 2023 TriSalus Life Sciences Inc., ("TriSalus" or the "Company"), an oncology company in the process of going public through a business combination transaction (the "Business Combination") with MedTech Acquisition Corporation (Nasdaq: MTAC) ("MedTech" or "MTAC"), reported new Phase 1 clinical data presented at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) ("AACR") 2023 Annual Meeting taking place in Orlando, Florida, from April 14-19, 2023 (Press release, TriSalus Life Sciences, APR 20, 2023, View Source [SID1234630359]).

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 clinical data presented at the AACR (Free AACR Whitepaper) 2023 Annual Meeting relates to the Company’s ongoing Pressure-Enabled Regional Immuno-Oncology ("PERIO-01") clinical study for uveal melanoma with liver metastases ("UMLM"). The PERIO-01 trial is studying an investigational class C toll-like receptor-9 agonist, SD-101, delivered intravascularly with the TriNav Infusion System ("TriNav") using the Pressure-Enabled Drug Delivery ("PEDD") method of administration. PERIO-01 is evaluating whether this platform approach can improve the performance of systemic checkpoint inhibitors in patients with UMLM.

PERIO-01 is an open-label, first-in-human Phase 1 trial of SD-101, given by hepatic arterial infusion with TriNav using PEDD in UMLM (NCT04935229). The study consists of dose-escalation cohorts of SD-101 (2, 4, or 8 mg) alone or with immune checkpoint inhibition ("ICI"). At data cutoff as of January 14, 2023, based on pooled data from 27 patients enrolled in the PERIO-01 trial, only 3 patients were treatment naïve, and others received 1-7 lines of prior therapy. Within these 27 patients, there has been one treatment-related serious adverse event. The most common treatment related adverse events overall were fatigue (9 events), abdominal discomfort (6 events), and dizziness (3 events) which were all graded as non-serious. Grade 3 liver function test elevations were noted in one subject, which was not clinically serious.

Circulating tumor cell and circulating tumor DNA ("ctDNA") levels were noted to decrease in 6 out of 13 patients and 6 out of 9 patients, respectively, based on available data. Decreases of ctDNA have been associated with longer overall survival in the stage IV uveal melanoma population. 5 out of 5 patients with available data demonstrated reductions in intratumoral myeloid derived suppressor cells ("MDSCs"), which the Company has previously demonstrated in pre-clinical liver metastasis models to be associated with immunosuppression. This data supports the hypothesis that checkpoint inhibitors in combination with SD-101 delivered via the PEDD method can enable broad immune effects, including the depletion of liver MDSCs.

"We believe our approach has the potential to improve outcomes and enhance the quality of life for patients with liver and pancreatic tumors receiving checkpoint inhibitor therapy," said Steven C. Katz, MD, FACS, Chief Medical Officer at TriSalus. "The data presented at the AACR (Free AACR Whitepaper) 2023 Annual Meeting shows that SD-101 has been well tolerated to date when administered via PEDD, at multiple dose levels alone and in combination with checkpoint inhibition. SD-101 infusions have also been associated with encouraging immunologic activity and ctDNA decreases, even at the lower doses, in heavily pre-treated patients. The serious adverse event rate related to treatment to date suggests that our delivery approach may enhance the therapeutic index for SD-101. We look forward to continuing our trials and adding to the growing body of evidence that our proprietary PEDD method is a potentially powerful approach for enabling SD-101 to improve efficacy of systemic immunotherapies like checkpoint inhibitors."

On April 20, 2023, TRACON Pharmaceuticals, Inc. (the "Company") reported to have entered into a third amendment with effect from April 15, 2023 (the "Loan Amendment") to the loan and security agreement, dated as of September 2, 2022 and amended as of December 22, 2022 and March 31, 2023 (the "RGC Loan Agreement"), by and among the Company, each party to the RGC Loan Agreement from time to time a borrower thereunder, the lenders from time to time a party thereto and Runway Growth Finance Corp., as administrative agent and collateral agent for the lenders ("Lender") (Filing, 8-K, Tracon Pharmaceuticals, APR 20, 2023, View Source [SID1234630358]). The Loan Amendment amends the RGC Loan Agreement to, among other things, provide for the following terms: on or before April 28, 2023, if the Company has raised at least $25.0 million in net cash proceeds from certain equity or debt transactions prior to making such request, Lender may, in its sole and absolute discretion, allow or deny loaning to the Company an aggregate principal amount of $10.0 million, with the full amount funded in a single disbursement. If the loan described above is not made by April 28, 2023, the maturity date will be April 28, 2023, the RGC Loan Agreement will terminate on that date, and the Company will not be obligated to pay the prepayment fee described in the RGC Loan Agreement but the final payment fee described in the RGC Loan Agreement will become immediately due and payable.

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!

All other material terms, including the interest-only period and covenants in the RGC Loan Agreement, remain unchanged.

The foregoing summary of the material terms of the Loan Amendment does not purport to be complete and is subject to, and qualified in its entirety by, the full text of the Loan Amendment, a copy of which will be filed with the Company’s Quarterly Report on Form 10-Q for the quarter ended June 30, 2023.

On April 20, 2023 Sensei Biotherapeutics, Inc. (Nasdaq: SNSE), an immuno-oncology company focused on the discovery and development of next-generation therapeutics for cancer patients, reported that the U.S. Food and Drug Administration (FDA) has cleared its Investigational New Drug (IND) application for SNS-101, a conditionally active VISTA-blocking antibody, paving the way for the Company to conduct a Phase 1/2 clinical trial in patients with solid tumors (Press release, Sensei Biotherapeutics, APR 20, 2023, View Source [SID1234630357]).

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!

"Receiving IND clearance to advance our first conditionally active antibody into a Phase 1/2 clinical trial represents an important milestone for Sensei. We believe that SNS-101 has the potential to make a significant impact in the field and to improve the lives of cancer patients worldwide," said John Celebi, President and Chief Executive Officer of Sensei Biotherapeutics. "We are delighted to bring SNS-101 into the clinic and explore its potential as a transformative treatment option for patients with solid tumors."

The Phase 1/2 clinical trial is designed to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and efficacy of SNS-101 as both a monotherapy and in combination with Regeneron’s PD-1 inhibitor Libtayo (cemiplimab) in solid-tumor cancer patients. The Phase 1 dose escalation portion of the clinical trial will be followed by an expansion Phase 2 in selected patient populations once a recommended Phase 2 dose is determined. SNS-101 will be administered as an intravenous infusion once every three weeks. Sensei expects to dose the first patient in mid-2023.

"Based on our preclinical data, we believe SNS-101 will be the first antibody to meaningfully explore the VISTA axis in the immuno-oncology space, with potential to achieve a higher therapeutic index and a more favorable tolerability profile than drugs limited by toxicity and poor pharmacokinetics," said Edward van der Horst, Ph.D., Chief Scientific Officer of Sensei.

SNS-101 is a conditionally active, human monoclonal IgG1 antibody designed to selectively block the VISTA checkpoint in the tumor microenvironment, which acts as a suppressor of T cells by binding the receptor PSGL-1. Preclinical studies have demonstrated SNS-101’s potential to inhibit tumor growth as monotherapy, significantly enhance the anti-tumor effects of PD-1 blockade, avoid poor pharmacokinetics from target-mediated drug disposition and lower the risk of cytokine release syndrome.