On May 22, 2023 TransCode Therapeutics, Inc. (NASDAQ: RNAZ) ("TransCode" or the "Company"), the RNA Oncology Company committed to more effectively treating cancer using RNA therapeutics, reported that its Board of Directors approved a 1-for-20 reverse stock split, to be effective 4:05 p.m. Eastern Time today, May 22, 2023 (Press release, TransCode Therapeutics, MAY 22, 2023, View Source [SID1234631922]). TransCode common stock is expected to begin trading on a split-adjusted basis on the Nasdaq Capital Market on Tuesday, May 23, 2023, under the current trading symbol, "RNAZ." The reverse stock split was approved by TransCode’s stockholders on May 10, 2023, and is intended to increase the per share trading price of the Company’s common stock to enable the Company to satisfy the minimum bid price requirement for continued listing on the Nasdaq Capital Market.

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The 1-for-20 reverse stock split will automatically convert 20 current shares of TransCode’s common stock into one new share of common stock. No fractional shares will be issued in connection with the reverse stock split. Stockholders of record who would otherwise hold a fractional share of TransCode’s common stock will receive a cash payment in lieu thereof at a price equal to that fraction of a share to which the stockholder would otherwise be entitled multiplied by the closing price of TransCode’s common stock on the Nasdaq Capital Market on May 22, 2023. The reverse split will reduce the number of shares of outstanding common stock from approximately 16,998,534 shares to approximately 849,926 shares. Proportional adjustments also will be made to the exercise prices of TransCode’s outstanding stock options and warrants, and to the number of shares issued and issuable under TransCode’s stock incentive plans.

Vstock Transfer LLC will act as the exchange agent for the reverse stock split. Stockholders of record are not required to take any action to receive post-split shares in book-entry. Stockholders owning shares through a bank, broker, custodian or other nominee will have their positions automatically adjusted to reflect the reverse stock split, subject to the holding entity’s particular processes; such stockholders will not be required to take any action in connection with the reverse stock split. However, these banks, brokers, custodians or other nominees may have different procedures than registered stockholders for processing the reverse stock split and making payment for fractional shares. If a stockholder holds shares of common stock with a bank, broker, custodian or other nominee and has any questions in this regard, stockholders are encouraged to contact their bank, broker, custodian or other nominee for more information.

In connection with the reverse stock split, the Company’s CUSIP number will change to 89357L 204 as of 4:05 pm on Monday, May 22, 2023.

On May 22, 2023Rain Oncology Inc. (NasdaqGS: RAIN), (Rain), a late-stage company developing precision oncology therapeutics with its lead product candidate, milademetan, an oral, small molecule inhibitor of the MDM2-p53 complex that reactivates p53, reported its topline pivotal Phase 3 MANTRA data (Press release, Rain Therapeutics, MAY 22, 2023, View Source [SID1234631921]). The trial, evaluating the efficacy, safety, and tolerability of milademetan in patients with dedifferentiated (DD) liposarcoma (LPS), did not meet its primary endpoint of progression free survival (PFS) by blinded independent central review compared to the standard of care, trabectedin.

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The median PFS for milademetan was 3.6 months vs 2.2 months for trabectedin, with a hazard ratio of 0.89, p=0.53. The most common treatment emergent adverse events (TEAEs) in the milademetan arm included nausea, thrombocytopenia, anemia, vomiting and neutropenia. The most common Grade 3/4 TEAEs were thrombocytopenia (39.5%), neutropenia (25.5%) and anemia (18.6%). Dose reductions in the milademetan arm were 44.2% vs 29.1% in the trabectedin arm. Discontinuation in the milademetan arm due to AEs were 11.6% vs 19.0% for trabectedin. Based upon these topline data, Rain does not expect to pursue further development of milademetan in DD LPS. Rain hopes to present the MANTRA data in an upcoming medical conference.

"We are very disappointed in the outcome of the MANTRA trial, as the results did not closely mirror prior clinical results in patients with DD LPS," said Avanish Vellanki, co-founder and chief executive officer of Rain. "We are truly saddened we will not likely be able to offer patients new treatment options for this challenging disease. However, the quality and robustness of the global MANTRA trial reflects an unambiguous data set. Rain’s mission remains to advance science, and therefore we will further evaluate the totality of the MANTRA data to support the scientific and medical community in the hope we can aid others in finding new strategies for patients with DD LPS. Based on the MANTRA topline results, we will also re-evaluate the path forward for milademetan. We continue to believe that reactivating p53 is an important avenue to pursue as part of a treatment strategy across cancer. I would like to extend our sincerest gratitude to the patients and clinicians who participated in the trial as well as our dedicated team."

Phase 3 MANTRA Topline Data Results:

· The median PFS was 3.6 months with milademetan versus 2.2 months for trabectedin, with a hazard ratio of 0.89 (95% CI [0.61 to 1.29]; p=0.53) based on 115 events
· Most common TEAEs in the milademetan arm included nausea, thrombocytopenia, anemia, vomiting and neutropenia
· The most common Grade 3/4 TEAEs in the milademetan arm were thrombocytopenia (39.5%), neutropenia (25.5%) and anemia (18.6%)
· Dose reductions in the milademetan arm were 44.2% vs 29.1% in the trabectedin arm
· Discontinuations in the milademetan arm due to AEs were 11.6% vs 19.0% for trabectedin
· Treatment emergent SAEs in the milademetan arm were 36.0% vs 48.1% in the trabectedin arm

The Rain management team will host a conference call today at 8:30 a.m. ET to discuss the topline data. The dial-in number for the conference call is 877-704-4453 for domestic participants and 201-389-0920 for international participants, with Conference ID: 13739033. A live webcast of the conference call can be accessed at the "Events" page on the Rain website, or by clicking here. A replay will be available shortly after conclusion of the event.

About MANTRA Trial

The MANTRA trial, a randomized, multicenter, open-label, Phase 3 registrational study, was designed to evaluate the safety and efficacy of milademetan compared to trabectedin, a current standard of care, in patients with unresectable or metastatic DD LPS with or without a WD LPS component that has progressed on one or more prior systemic therapies, including at least one anthracycline-based therapy. 175 patients were enrolled and randomized in a 1:1 ratio to receive milademetan or trabectedin. The primary objective of the trial was to compare PFS by blinded independent central review between the milademetan treatment arm and the trabectedin control arm. Secondary endpoints included overall survival, PFS by investigator assessment, objective response rate, duration of response, disease control rate, safety and patient reported outcomes.

About Milademetan

Milademetan (also known as RAIN-32) is an oral small molecule inhibitor of the MDM2-p53 complex that reactivates p53. Milademetan has demonstrated antitumor activity in an MDM2-amplified subtype of liposarcoma (LPS) and other solid tumors in a Phase 1 clinical trial, supported by a rationally designed dosing schedule to mitigate safety concerns and widen the potential therapeutic window of inhibition of the MDM2-p53 complex. Rain has completed its Phase 3 trial of milademetan (MANTRA) in patients with LPS, and is evaluating milademetan in a Phase 2 tumor-agnostic basket trial in certain solid tumors with MDM2 amplification (MANTRA-2). Rain anticipates commencing a Phase 1/2 clinical trial to evaluate the safety, tolerability and efficacy of milademetan in combination with Roche’s atezolizumab in patients with loss of cyclin-dependent kinase inhibitor 2A (CDKN2A) and wildtype p53 advanced solid tumors (MANTRA-4), in mid-2023. Milademetan has received Orphan Drug Designation from the U.S. Food and Drug Administration (FDA) for the treatment of LPS.

On May 22, 2023 Panbela Therapeutics, Inc. (Nasdaq: PBLA), a clinical stage company developing disruptive therapeutics for the treatment of patients with urgent unmet medical needs, reported that it has entered into a clinical trial agreement with Moffitt Cancer Center for a Phase I/II program in STK11 mutant non-small cell lung cancer (NSCLC) (Press release, Panbela Therapeutics, MAY 22, 2023, View Source;utm_medium=rss&utm_campaign=panbela-announces-clinical-trial-with-moffitt-cancer-center-for-phase-i-ii-program-in-stk11-mutant-non-small-cell-lung-cancer [SID1234631919]). The initial goal of the Phase I trial will be to ascertain the maximum tolerated dose of eflornithine, while evaluating efficacy and then moving into a Phase II efficacy trial. We anticipate data from the Phase I trial by the end of this year with a look to start the Phase II trial at the end of the year or early 2024.

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"The relationship between polyamines and the immune system has been highlighted in peerreviewed journals. This clinical trial with Moffitt seeks our first clinical proof of concept to evaluate the modulation of the immune system by polyamines in combination with standard of care cancer therapy," said Jennifer K. Simpson, PhD, MSN, CRNP, President & Chief Executive Officer of Panbela. "The STK11 mutant NSCLC population has historically had a poor response to checkpoint inhibitor therapy. If the trial is successful, it opens the door for combining polyamine targeted therapies, such as eflornithine and ivospemin, with checkpoint inhibitors in other tumor types where response rates have been poor, or even improve upon reasonable response rates. It would also open the possibility of exploring combinations of eflornithine and ivospemin with other immunotherapies, such as CAR-T therapy."

"There is a huge unmet need for new therapies for STK11 mutant non-small cell lung cancer patients, given their low survival rates. We know that STK11 mutant tumors have reduced levels of T cells that direct immune surveillance, and they can avoid immune detection. We are excited to partner with Panbela to determine if modulating polyamines can restimulate the immune system to target these hard-to-treat tumors." said Jhanelle Gray, M.D., lead investigator of the trial, Chair of Moffitt’s Department of Thoracic Oncology and Co-Leader of Moffitt’s Molecular Medicine Program.

On May 22, 2023 Oncorus, Inc. (Nasdaq: ONCR), an RNA medicines company focused on developing intravenously administered, self-amplifying RNA to transform outcomes for cancer patients, reported its first quarter financial results and provided an update on its business (Press release, Oncorus, MAY 22, 2023, View Source [SID1234631918]).

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"Oncorus is pioneering a first-of-its-kind, self-amplifying RNA platform with an exciting lead program, ONCR-021, with plans to submit an IND with the FDA in mid-2023," said Theodore (Ted) Ashburn, M.D., Ph.D., President and Chief Executive Officer of Oncorus. "Our exceptional team continues to drive our mission of realizing the full promise of IV-administered RNA medicines for cancer patients."

Business Highlights

Progressed Self-amplifying RNA platform. Oncorus still plans to submit an investigational new drug application (IND) for ONCR-021, the lead product candidate from its self-amplifying RNA platform, in mid-2023, subject to receipt of additional funding for continued clinical development of the program. The company plans to evaluate ONCR-021 in patients with non-small cell lung cancer, renal cell carcinoma, melanoma, hepatocellular carcinoma and anaplastic thyroid cancer.
Appointment of Interim Chief Financial Officer. On May 9, 2023, Oncorus appointed Alexander Nolte as its interim Chief Financial Officer. Prior to joining Oncorus, Mr. Nolte served as Vice President, Chief Accounting Officer, at Syndax Pharmaceuticals. Prior to Syndax, he served as Corporate Controller at CoLucid Pharmaceuticals, Inc. until its acquisition by Eli Lilly. Earlier in his career, Mr. Nolte held various positions within the finance functions of Aegerion Pharmaceuticals and Genzyme Corporation. Mr. Nolte began his professional career at KPMG Accountant NV in the Netherlands and PricewaterhouseCoopers LLP.
Payoff of Debt Capital Facility with K2 HealthVentures. On May 12, 2023, Oncorus prepaid approximately $21.6 million to K2 HealthVentures LLC (K2HV), its senior lender, in full satisfaction of all obligations, including all outstanding principal, accrued interest, fees, costs, expenses and other amounts chargeable under the Loan and Security Agreement, dated April 1, 2022, by and between Oncorus and K2HV. The payoff terms provided for the termination of all commitments and obligations under the Loan and Security Agreement and related documents and the release of all liens held by K2HV on Oncorus’ assets.
First Quarter 2023 Financial Results

Cash, cash equivalents and investments totaled $45.0 million as of March 31, 2023 compared to $62.2 million as of December 31, 2022.

Research and development expenses for the quarter ended March 31, 2023 were $10.6 million compared to $12.5 million for the corresponding quarter in 2022. The decrease was primarily attributable to the reduction in direct external expenses for ONCR-177 in connection with the winding down of the program and the reduction in employee compensation costs, primarily due to employee turnover and decreased fulltime headcount.

General and administrative expenses for the quarter ended March 31, 2023 were $4.5 million compared to $5.3 million for the corresponding quarter in 2022. The decrease was primarily attributable to the reduction in employee compensation and related expenses, primarily due to employee turnover and decreased fulltime headcount and a decrease in professional service and consultant fees primarily related to decreased consultant costs and decreased recruiting costs.

Net loss for the quarter ended March 31, 2023 was $30.9 million, or $1.18 per share, as compared to a net loss of $17.8 million, or $0.69 per share for the corresponding quarter in 2022. The decrease in net loss was primarily due a long-lived asset impairment charge of $14.6 million taken on March 31, 2023 and lower research and development and general and administrative expenses, as described above.

Financial Guidance

Oncorus expects its cash, cash equivalents and investments, following the full prepayment of its debt capital facility with K2HV in May 2023, to fund its operations into the third quarter of 2023. The foregoing estimate does not give effect to potential business development opportunities or additional financing activities.

On May 22, 2023 NeuBase Therapeutics, Inc. (Nasdaq: NBSE) ("NeuBase" or the "Company"), a biotechnology company developing Stealth Editors to perform in vivo gene editing without triggering the immune system, reported a broad set of preclinical safety and efficiency data for its Stealth Editors development program that demonstrate the ability to achieve gene editing with a non-immunogenic system (Press release, NeuBase Therapeutics, MAY 22, 2023, View Source [SID1234631917]).

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These preclinical data were featured in an oral presentation by Dr. Dani Stoltzfus, Vice President of Research at NeuBase, titled, "Nuclease-Free Gene Editing with Peptide Nucleic Acids: A New Class of In Vivo Gene Editors," at the ASGCT (Free ASGCT Whitepaper) 2023 Annual Meeting.

"We are excited to announce preclinical data from our Stealth Editors development program that were presented during the ASGCT (Free ASGCT Whitepaper) 2023 Annual Meeting. These data support our novel in vivo gene editing approach that allows us to tag a locus in the genome that harbors a mutation with a simple synthetic compound and recruit the cell’s own machinery to repair the mutation. This high-fidelity non-immunogenic approach is expected to offer advantages compared to modified bacterial CRISPR/Cas enzymes for in vivo gene editing applications from a safety and durability of effect perspective," stated Dietrich A. Stephan, Ph.D., Founder and Chief Executive Officer of NeuBase. "We continue to rapidly advance the development of our Stealth Editors platform, which we believe has the potential to generate best-in-class, next-generation therapies capable of addressing diverse types of high-value genetic mutations. Throughout the remainder of 2023, we expect to announce additional preclinical data from several ongoing and planned studies in non-human primates and mice."

"Taken together, these data indicate that our novel synthetic gene editing technology is promising and can be encapsulated into delivery technologies that have delivered payloads to patients in the marketplace with known performance characteristics, enabling us to have a risk-off stance to delivery. Furthermore, the data presented at the ASGCT (Free ASGCT Whitepaper) 2023 Annual Meeting illustrates that we can edit genes, the non-immunogenic nature of our editing system, and the exquisite fidelity of human DNA repair enzymes, all of which are the essential ingredients for a winning in vivo editing solution," concluded Dr. Stephan.

Overview of Preclinical Studies and Results Presented at ASGCT (Free ASGCT Whitepaper) 2023 Annual Meeting:

Ex vivo editing with Stealth Editors – The Company investigated the capabilities of a new editing system to effectively edit human cells ex vivo. The editing system is comprised of two synthetic reagents: a modified peptide nucleic acid and an oligonucleotide donor molecule. Human cells were modified to contain a fluorometric reporter system that allows rapid and real-time colorimetric readout of correction of a frameshift mutation in the genome. The result of the studies showed a dose-dependent increase in correction of the gene mutation based on expression of the newly functional fluorescent protein compared with various controls, highlighting a titratable increase in efficiency with which the Stealth Editors can engage the genome to harness the cell’s own machinery to correct the mutation. The Company has made strides toward increasing editing efficiency over the past months and believes efficiency will continue to increase with technical improvements. This ex vivo fluorometric system is rapidly modifiable to include any gene editing target of interest and allow rapid screening against diverse targets to identify hits, supporting both the Company’s emerging in-house pipeline of therapeutic programs, which the Company plans to announce later this year, as well as potential research partnerships.

Proven Non-Immunogenic profile in human peripheral blood mononuclear cells ("PBMCs") – The Company demonstrated the stealth nature of its editing solution with PBMCs from multiple donors treated with either known immunostimulants or Stealth Editors packaged inside a lipid nanoparticle. The results of this study show PBMCs treated with a Stealth Editor did not impact cell viability. In addition, there was no cellular immune response for the Stealth Editor-treated cells compared with the control (PBS) across the five cytokines measured, in direct juxtaposition to the positive controls, which elicited a strong cytokine response. The conclusion from these data is that Stealth Editors do not elicit innate immune responses in the encapsulated format in which they would be administered systemically, and the Company believes this is likely to be an important differentiator of its technology when transitioned to in vivo gene editing.

Delivered via Non-Immunogenic Delivery Technology – Using clinically-validated technology, the Company has generated Stealth Editor lipid nanoparticles (LNP) where the hydrodynamic diameter is approximately 70 nm, and the polydispersity index is <0.1. Furthermore, the Company’s drug product has a physiologically acceptable pH of 7.3 and an osmolality in the range of 300. These data demonstrate that NeuBase has overcome the challenge of how to encapsulate Stealth Editors and sets the stage to move this program into in vivo studies.
Myotonic Dystrophy Type 1 (DM1) Program Data at ASGCT (Free ASGCT Whitepaper) 2023 Annual Meeting

In addition, during the ASGCT (Free ASGCT Whitepaper) 2023 Annual Meeting, the Company presented data from its Myotonic Dystrophy Type 1 (DM1) program in an oral presentation titled, "Toxicology, Pharmacokinetics and Biodistribution of a PATrOL-Enabled Investigational Genetic Therapy for Myotonic Dystrophy, Type 1." The slide presentations for the Stealth Editors and DM1 data updates at the ASGCT (Free ASGCT Whitepaper) 2023 Annual Meeting will be made available on the Publications and Presentations section of the NeuBase website (click here).

Conference Call and Webcast

The Company’s management team will host a conference call and webcast with investors and analysts to discuss the data presented at the ASGCT (Free ASGCT Whitepaper) 2023 Annual Meeting on Monday, May 22, 2023, at 8:30 am ET. The live call may be accessed by dialing (877) 407-9208 for domestic callers and (201) 493-6784 for international callers and entering the conference ID: 13738958. The live webcast presentation with accompanying slides will be accessible here and on the Investor Relations Calendar page of the Company’s website at View Source Following the completion of the event, a replay will be available on the Company’s website.