On April 8, 2022 Oncorus, Inc. (Nasdaq: ONCR), a viral immunotherapy company focused on driving innovation to transform outcomes for cancer patients, reported its presentation of preclinical data for both ONCR-021 and ONCR-788 in two e-posters at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2022, taking place April 8-13 in New Orleans, Louisiana, supporting the company’s selectively self-amplifying viral RNA (vRNA) Immunotherapy Platform (Press release, Oncorus, APR 8, 2022, View Source [SID1234611670]).

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"The preclinical data presented on ONCR-021 and ONCR-788 at AACR (Free AACR Whitepaper) are an important step forward for Oncorus’ novel approach of selectively self-amplifying vRNA immunotherapies formulated in lipid nanoparticles. We are incredibly pleased to see these vRNA drug candidates’ potent efficacy in preclinical tumor models, after intravenous administration of the nanoparticle formulation even in the presence of neutralizing antibodies," said Ted Ashburn, M.D., Ph.D., President and Chief Executive Officer of Oncorus. "These data further bolster our confidence in our vRNA platform’s ability to deliver the RNA genome of oncolytic viruses to tumors intravenously and to circumvent the common limitation of existing IV-administered oncolytic viral cancer therapies. We look forward to advancing this next-generation approach of selectively self-amplifying vRNA, furthering our goal of realizing the full potential of systemically active viral immunotherapies to transform outcomes for cancer patients."

Oncorus’ vRNA Immunotherapy Platform encapsulates the genomes of RNA viruses known to kill cancer cells within an LNP, producing a living oncolytic and immunostimulatory viral infection in the tumor to destroy cancer cells and stimulate the immune system. In preclinical studies, Oncorus’ IV-administered vRNA immunotherapies demonstrated efficacy in multiple tumor models, avoiding the challenges seen in previous studies incorporating IV administration of RNA-based oncology therapeutics.

In a poster titled, "ONCR-021 as a systemic intravenous synthetic RNA virus immunotherapy for the repeat treatment of cancer," Oncorus highlighted:

ONCR-021, Oncorus’ lead vRNA immunotherapy product candidate, is an LNP formulation of Coxsackievirus A21 (CVA21) vRNA, which encodes an optimized strain of CVA21.
ONCR-021 demonstrated greater in vitro and in vivo oncolysis compared to previously described CVA21 Kuykendall strain.
IV administration of ONCR-021 vRNA resulted in rapid initiation of viral replication, oncolysis and potent anti-tumor efficacy driven by CVA21 amplification in situ after delivery to tumor cells.
Preclinical data support the potential clinical development of ONCR-021 in non-small cell lung cancer (NSCLC), renal cell carcinoma (RCC) and melanoma based on viral tropism.
Oncorus plans to submit an investigational new drug (IND) application for ONCR-021 with the U.S. Food and Drug Administration (FDA) in mid-2023.

In a poster titled, "Development of ONCR-788, a synthetic oncolytic virus based on Seneca Valley Virus for the treatment of neuroendocrine tumors," Oncorus highlighted:

ONCR-788, Oncorus’ second vRNA immunotherapy product candidate, encodes an optimized version of the Seneca Valley Virus (SVV).
Systemic IV administration of ONCR-788 led to potent anti-tumor efficacy, even in the presence of oncolytic virus neutralizing antibodies within the bloodstream.
vRNA delivery, viral replication, spread and lysis of tumor cells were observed after administration of ONCR-788.
Robust anti-tumor efficacy was observed across a diverse set of neuroendocrine tumor models, including tumor CDX and PDX xenografts, lung orthotopic and GEMM-derived models.
Enhanced T cell recruitment and activation, increased expression of PD-L1 on tumor cells and myeloid cells and M2 to M1 macrophage conversion were observed.
ONCR-788 in combination with an anti-PD1 resulted in improved anti-tumor activity as compared to ONCR-788 monotherapy.
Oncorus plans to submit an IND for ONCR-788 with the FDA following the IND submission for ONCR-021.

The posters presented at AACR (Free AACR Whitepaper) are available on the "Publications & Presentations" section of the Oncorus website at www.oncorus.com.

On April 8, 2022 OnKure, Inc., a clinical-stage biopharmaceutical company discovering and developing the next generation of oncology precision medicines, reported preclinical data demonstrating synergy between OKI-179, the Company’s oral Class I histone deacetylase (HDAC) inhibitor, and RAS pathway agents, including Pfizer’s MEK inhibitor, binimetinib, in RAS-mutated tumor models (Press release, OnKure, APR 8, 2022, View Source;utm_medium=rss&utm_campaign=onkure-therapeutics-announces-promising-preclinical-data-on-oki-179-in-ras-mutated-tumor-models-presented-in-a-late-breaking-session-at-aacr [SID1234611669]). The data will be disclosed in a late-breaking abstract during the American Association of Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting, being held in New Orleans, Louisiana from April 8, 2022 to April 13, 2022.

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"The preclinical data highlighting our HDAC inhibitor’s synergy with RAS pathway agents are extremely promising, and based on the anti-tumor activity seen, strongly support the clinical development of this combination across multiple indications, including in cancer types less sensitive to RAS pathway inhibition alone," said Tony Piscopio, Ph.D., Co-Founder, President and Chief Executive Officer of OnKure. "OKI-179 has been designed to overcome the historic tolerability limitations of other HDAC inhibitors, supporting further development in rational combinations with other anti-cancer treatments. Since inhibition of the RAS pathway alone through MEK or BRAF inhibitors is often insufficient to drive tumor regression, it opens an opportunity for combination approaches with OKI-179, with the potential to establish this candidate as a backbone therapy for all RAS-mutated cancers."

The data, both in vitro and in vivo, showcase the potential of the synthetically lethal combination of OKI-179 and RAS pathway agents in treating RAS-mutated tumors. In cell-line derived xenograft models, OKI-179, binimetinib as a single agent, and binimetinib + encorafenib combination demonstrated tumor growth delay, but few regressions. OKI-179 combined with binimetinib in NRAS-mutated melanoma or combined with binimetinib + encorafenib in BRAF-mutated colorectal xenografts showed significantly increased regressions compared to either single agent following two weeks of dosing.

Jennifer Diamond, M.D., OnKure’s Chief Medical Officer said, "We plan to initiate the Nautilus trial, which will explore the combination of OKI-179 and binimetinib in advanced NRAS-mutated melanoma, and look forward to continuing to validate this synthetically lethal combination across cancer types in order to fully understand its potential as a therapeutic approach."

The poster presentation from the AACR (Free AACR Whitepaper) Annual Meeting is available on the "Publications" page of the Company’s website at View Source

About NRAS-Mutated Melanoma

Activating mutations in NRAS is the second most common oncogenic driver in melanoma, accounting for 20% of all melanomas. Tumors bearing NRAS mutations are more aggressive and are associated with poorer patient outcomes. Despite the prevalence of NRAS mutations and the severity of the resulting disease, treatment options for NRAS-mutated melanoma remain limited for patients who have disease progression following immune checkpoint inhibitor therapy, highlighting the significant unmet need.

About OKI-179

OKI-179 is a novel, oral Class I histone deacetylase (HDAC) inhibitor for the potential treatment of a wide range of solid and hematological malignancies. HDAC inhibitors have shown little activity in treating solid tumors, often due to poor tolerability, inappropriate dosing regimens, and a lack of stratifying biomarkers. OKI-179 is designed to have improved potency, selectivity, tolerability, as well as easy combinability to overcome the historic limitations of other HDAC inhibitors. This candidate has also shown a promising safety profile in advanced solid tumor patients, supporting potential combination studies in the future.

On April 8, 2022 Bicycle Therapeutics plc (NASDAQ: BCYC), a biotechnology company pioneering a new and differentiated class of therapeutics based on its proprietary bicyclic peptide (Bicycle) technology, reported that interim Phase I results from the Phase I/II trial of BT8009, a second-generation BTC targeting Nectin-4, will be presented at the 2022 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting, being held April 8-13, 2022 in New Orleans, LA (Press release, Bicycle Therapeutics, APR 8, 2022, View Source [SID1234611668]). The Company will host a conference call to discuss the data from the presentation on Monday, April 11, 2022 at 8:30 a.m. ET.

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Oral Presentation Details

Title: BT8009-100 Phase I/II Study of Novel Bi-Cyclic Peptide and MMAE Conjugate BT8009 in Patients with Advanced Malignancies Associated with Nectin-4 Expression
Abstract #: CT025
Presenter: Meredith McKean, Sarah Cannon Research Institute at Tennessee Oncology
Session Title: Biomarker Advances in Clinical Trials
Date/Time: Sunday, April 10, 2022 at 4:05 – 4:15 p.m. CT

The abstract can now be viewed here.

Conference Call Details

Bicycle Therapeutics will host a conference call and webcast on Monday, April 11, 2022 at 8:30 a.m. ET to review the data being presented. To access the call, please dial (800) 377-9118 (domestic) or (409) 937-8920 (international) and provide the Conference ID 2775710. A live webcast of the presentation will be available on the Investors & Media section of the Bicycle website, bicycletherapeutics.com.

On April 8, 2022 Orum Therapeutics, a private biotechnology company pioneering the development of tumor-directed targeted protein degraders (TPDs), reported that preclinical data for ORM-5029, a potential first-in-class TPD therapy for HER2-positive cancers, at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) ("AACR") Annual Meeting 2022 (Press release, Orum Therapeutics, APR 8, 2022, View Source [SID1234611667]). ORM-5029 is one of two lead programs from the company’s Antibody neoDegrader Conjugate (AnDC) platform based on its Dual-Precision Targeted Protein Degradation (TPD²) approach.

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ORM-5029 is designed to selectively deliver catalytic GSPT1 protein degraders to HER2-expressing tumor cells via antibody targeting. Orum developed a proprietary class of GSPT1 degrader molecules, paired them with a HER2-targeting antibody, pertuzumab, and screened numerous candidate conjugates to identify a molecule with the desired therapeutic profile. The data presented at AACR (Free AACR Whitepaper) 2022 describes initial preclinical evaluation of potency, efficacy, and pharmacodynamic (PD) response of ORM-5029.

"Targeted protein degradation holds much therapeutic promise, but classic TPD approaches face clinical development hurdles, including optimizing potency, exposure, and tolerability," said Peter U. Park, Ph.D., Chief Scientific Officer of Orum Therapeutics. "We believe that we can fulfill the promise of TPD by developing novel small molecule degraders combined with the precise cellular delivery mechanism of antibodies. Compared to either small molecule GSPT1 degraders or standard-of-care antibody drug conjugates, ORM-5029 exhibited superior in vitro and in vivo potency, robust efficacy in low-HER2 settings, and dose-dependent efficacy. These data provide compelling evidence to support our unique approach to targeted protein degradation and continue development of ORM-5029."

Key data takeaways:

ORM-5029 displays robust efficacy both in vitro and in vivo compared to other small molecule GSPT1 degraders and approved antibody drug conjugates (ADCs)

ORM-5029 exhibits potent activity in HER2-low models both in vitro and in vivo

Dose-dependent efficacy of ORM-5029 correlates with robust and rapid PD modulation of tumor GSPT1 protein levels

Orum’s proprietary payload, SMol006, is a potent degrader with high selectivity for GSPT1 and is compatible with any ADC linker and conjugation technologies.

AACR 2022 is taking place both virtually and in-person at the Ernest N. Morial Convention Center in New Orleans from April 8-13. The poster presentation titled, "ORM-5029: A first-in-class targeted protein degradation therapy using antibody neodegrader conjugate (AnDC) for HER2-expressing breast cancer," will be available for viewing to registered attendees from Friday, April 8, through Wednesday, July 13, on the AACR (Free AACR Whitepaper) Annual Meeting 2022 website. The poster (abstract # 3933) will be presented in person on April 13 from 9:00 am to 12:30 pm in Session PO.ET06.06 – Emerging New Anticancer Agents in Exhibit Halls D-H, Poster Section 22, Poster Number 7.

The poster is available on request; please email us at [email protected].

About Orum’s AnDC Platform

Orum’s Antibody neoDegrader Conjugate (AnDC) platform uses the Company’s unique Dual-Precision Targeted Protein Degradation (TPD²) approach to build novel targeted protein degraders (TPD) combined with the precise tumor cell delivery mechanisms of antibodies to generate innovative, first-in-class cell-specific TPD for the treatment of cancer. The company has developed new molecular glue degrader payloads to specifically degrade an intracellular target protein within cancer cells via the E3 ubiquitin ligase pathway. Conjugated to antibodies, neoDegraders are designed to be delivered specifically to cancer cells and degrade the intracellular target protein and cause tumor cell death.

On April 8, 2022 Rubius Therapeutics, Inc. (Nasdaq: RUBY), a clinical-stage biopharmaceutical company that is biologically engineering red blood cells to create an entirely new class of cellular medicines called Red Cell Therapeutics for the treatment of cancer and autoimmune diseases, reported updated clinical data from the ongoing monotherapy Phase 1 arm of the Phase 1/2 clinical trial of RTX-240 in patients with advanced solid tumors at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting (Press release, Rubius Therapeutics, APR 8, 2022, View Source [SID1234611666]). The Company is hosting a webcast to discuss these data as well as data from the monotherapy Phase 1 arm of RTX-240 in patients with acute myeloid leukemia (AML) today at 1:15 p.m. EDT.

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"Recent advances in immuno-oncology have transformed the treatment of cancer and improved outcomes for certain patients. Yet, of the estimated 40 percent of patients eligible for immunotherapy, the majority do not have durable responses. In addition, combinations of immune checkpoint inhibitors have higher toxicity, underscoring the need for safer and more effective immunotherapy combination treatments," said Alexander I. Spira, M.D., Ph.D., FACP, director of the Virginia Cancer Specialists Research Institute and the Phase 1 Trial Program, and a clinical investigator in all of Rubius’ oncology clinical trials. "In this Phase 1 trial of heavily pretreated patients with advanced solid tumors, RTX-240 demonstrated single-agent activity with encouraging tolerability results, including in patients whose disease had progressed on prior PD-1/PD-L1-based treatment regimens. Based on these data, I believe RTX-240 has the potential to be an ideal candidate to be developed as a combination therapy with immune checkpoint inhibitors, especially in earlier lines of therapy."

"We believe the encouraging results of monotherapy RTX-240 reported provide clinical support of the RED PLATFORM and the development of our entire oncology pipeline of Red Cell Therapeutics given the programmable nature of our platform," said Pablo J. Cagnoni, M.D., president and chief executive officer. "With multiple data milestones expected over the next 12 months, Rubius Therapeutics’ pipeline of oncology Red Cell Therapeutics has the opportunity to show potential benefit in additional types of cancer."

Updated Data from the Phase 1 Trial of RTX-240 in Patients with Advanced Solid Tumors

Nine dose cohorts (n=34) were completed in the monotherapy solid tumor arm of the trial at the time of the data cutoff on March 4, 2022, with 34 patients evaluable for safety (primary outcome measure) and 27 patients evaluable for efficacy (secondary outcome measure). Enrollment continues in the 5e10 Q3W dose cohort.

As of the cutoff date, disease control was observed in 10 patients (1 partial response, 2 unconfirmed partial responses and 7 with stable disease), 9 of whom had experienced disease progression on prior anti-PD-1/anti-PD-L1 therapy.

There were three best responses of partial response (PR) in non-small cell lung cancer (NSCLC), anal cancer and uveal melanoma patients:​

An unconfirmed PR (uPR) with 41% decrease of all target lesions and a notable decrease of an external protruding chest wall mass in a patient with non-small cell lung cancer (NSCLC) whose disease had progressed on prior anti-PD-L1 therapy;
A confirmed PR with a 54% reduction in the target lesions in a patient with metastatic anal cancer whose disease had progressed on anti-PD-L1 therapy; and
An uPR with 100% decrease of the target hepatic lesion and resolution of multiple non-target hepatic lesions in a patient with metastatic uveal melanoma whose disease had progressed on anti-PD-1 therapy.
Stable disease was observed in 5 patients, including 3 with metastatic NSCLC and 2 with renal cell carcinoma (RCC) across the 3e10 cohorts, supporting the Company’s decision to expand the Phase 1 arm of RTX-240 plus pembrolizumab to NSCLC and RCC patients. One patient each with NSCLC and RCC remained on monotherapy treatment with SD greater than 6 months as of the cutoff date.​

As of the cutoff date, RTX-240 has been shown to have been generally well tolerated with no treatment-related or investigator-identified immune-related Grade 3/4 adverse events (AEs) and no dose-limiting toxicities.

Based on the totality of clinical, tolerability and pharmacodynamic data, a recommended monotherapy Phase 2 dose of 5e10 cells administered every 3 weeks was selected. This dose will be further explored in the combination expansion cohort of NSCLC and RCC patients.

"Immune agonists and cytokines have been the focus of oncology research given their known importance for immune activation. However, current approaches have been unable to overcome toxicity challenges, resulting in a narrow therapeutic index, particularly in combination with checkpoint inhibitors. With today’s updated clinical data showing that RTX-240 generated clinical responses with favorable tolerability results in patients whose tumors had progressed on therapy with anti-PD-1/PD-L1 antibodies, we believe these data support the potential of immune agonists for the treatment of cancer," said Larry Turka, M.D., chief scientific officer and head of translational medicine at Rubius Therapeutics. "Given the clinical results observed, we are expanding the ongoing Phase 1 arm of RTX-240 in combination with pembrolizumab to patients with NSCLC and RCC who have had fewer prior treatment regimens. This cohort is expected to inform our strategy of advancing RTX-240 in combination with pembrolizumab in a Phase 2 clinical trial."

Final Phase 1 Clinical Results in Relapsed/Refractory AML

Rubius also announced final clinical results from the Phase 1 arm of monotherapy RTX-240 in relapsed/refractory AML. As of the cutoff date of March 4, 2022, seventeen patients were enrolled across 4 dose levels. No DLTs were observed and there were 3 treatment-related Grade 3/4 adverse events. There were no investigator-reported immune-related AEs. Five patients had SD greater than 3 months, and 1 patient had a significant blast count reduction (53% to 6%).

"In this study, RTX-240 has shown activation and expansion of NK and T cells with favorable safety results, which continues to support the proposed mechanism of action of RTX-240. Based on these data, we believe RTX-240 could improve outcomes for AML patients when used as maintenance therapy for patients in remission following high-dose chemotherapy and stem cell transplantation," continued Dr. Turka. "Based on these data, we believe we have established the necessary foundation to evaluate RTX-240 in the maintenance setting for the treatment of AML. However, to focus our resources on advancing RTX-240 in combination with pembrolizumab in NSCLC and RCC, we do not plan to pursue a separate clinical trial in AML in the near-term."

Upcoming Anticipated Milestones

To evaluate the full potential of RTX-240, Rubius’ other oncology programs and the RED PLATFORM, Rubius plans to execute several critical milestones within the next 12 months and has sufficient cash runway into the second half of 2023:

Report initial Phase 1 clinical results for RTX-321 for the treatment of HPV 16-positive cancers during the second half of 2022;
Report initial Phase 1 clinical results for RTX-240 in combination with pembrolizumab in advanced solid tumors and data from the additional NSCLC and RCC patients in the second half of 2022;
Select a clinical candidate for the first autoimmune program in type 1 diabetes during the second half of 2022; and
Report initial Phase 1 clinical results for RTX-224 for the treatment of advanced solid tumors during the first quarter of 2023.
AACR Poster Presentation

Abstract Title: Phase 1 Trial of RTX-240, Allogeneic Red Blood Cells Engineered to Express 4-1BBL and Trans-Presented IL-15, in Patients with Advanced Solid Tumors
Session Title: Phase I Clinical Trials 2
Session Date and Time: Tuesday, April 12, 2022, 9:00 a.m. – 12:30 p.m. ET
Location: New Orleans Convention Center, Exhibit Halls D-H, Poster Section 33
Poster Board Number: 12
Abstract Number: CT187

Conference Call

The Company will host a conference call and webcast at 1:15 p.m. EDT to discuss this update. The audio webcast will be available on the Events and Presentations page within the Investors and Media section of the Rubius Therapeutics website. The update may also be accessed by dialing (800) 289-0045 (domestic) or (615) 622-8086 (international) five minutes prior to the start of the call. The conference ID is 7865329. An archived webcast will be accessible for 90 days after the event.

About RTX-240

RTX-240, Rubius Therapeutics’ lead oncology program, is an allogeneic, off-the-shelf cellular therapy product candidate that is engineered to simultaneously present hundreds of thousands of copies of the costimulatory molecule 4-1BB ligand (4-1BBL) and IL-15TP (trans-presentation of IL-15 on IL-15Rα) in their native forms. RTX-240 is designed to broadly stimulate the immune system by activating and expanding both NK and memory T cells to generate a potent anti-tumor response.

About the RTX-240 Clinical Trial

The Phase 1/2 clinical trial of RTX-240 is an open label, multicenter, multidose, first-in-human dose-escalation and expansion study designed to evaluate the safety and tolerability, pharmacokinetics, maximum tolerated dose, a recommended Phase 2 dose and dosing regimen of RTX-240. The trial is also assessing the pharmacodynamics of RTX- 240 measured by changes in T and NK cell number and function relative to baseline and anti-tumor activity. The trial has three separate Phase 1 arms: a monotherapy dose escalation arm in adults with relapsed/refractory or locally advanced solid tumors, a monotherapy dose escalation arm in adults with relapsed/refractory acute myeloid leukemia, and a combination therapy dose escalation arm with pembrolizumab in adults with relapsed/refractory or locally advanced solid tumors.