On April 15, 2024 Viracta Therapeutics, Inc. (Nasdaq: VIRX), a clinical-stage precision oncology company focused on the treatment and prevention of virus-associated cancers that impact patients worldwide, reported positive topline results from Stage 1 of the pivotal Phase 2 NAVAL-1 trial from both arms of the relapsed or refractory (R/R) Epstein-Barr virus-positive (EBV+) peripheral T-cell lymphoma (PTCL) cohort (Press release, Viracta Therapeutics, APR 15, 2024, View Source [SID1234642075]). Patients were randomized to either nanatinostat monotherapy (n=10) or to nanatinostat in combination with valganciclovir (Nana-val, n=10). These data were featured in an oral presentation during the 2024 Joint Annual Congress of Taiwan Society of Blood and Marrow Transplantation and The Hematology Society of Taiwan.

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"Nana-val demonstrated an impressive clinical response in patients with relapsed or refractory EBV-positive PTCL with a generally manageable safety profile, including one patient who was able to proceed to allogeneic stem-cell transplant and remains in response for over 8 months to date," said Hung Chang, M.D., Professor of Hematology, Linkou Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taoyuan, Taiwan and principal investigator in the NAVAL-1 trial. "The substantially greater clinical efficacy of Nana-val relative to nanatinostat monotherapy suggests that both agents in the combination regimen are contributing to its anti-tumor activity as predicted by their mechanisms of action. Nana-val is emerging as a promising, generally well-tolerated, convenient all-oral treatment for patients with relapsed or refractory EBV-positive PTCL."

Darrel P. Cohen, M.D., Ph.D., Chief Medical Officer of Viracta added, "Patients with relapsed or refractory EBV-positive PTCL have a very poor prognosis, worse than those with EBV-negative disease, yet there are presently no EBV-targeted treatment options available. We are encouraged by the Stage 1 data from patients with relapsed or refractory EBV-positive PTCL in the pivotal Phase 2 NAVAL-1 trial that further validates Nana-val’s differentiated ‘Kick and Kill’ mechanism of action. Building on these promising clinical outcomes emerging from the NAVAL-1 trial, which are consistent with those from our preceding Phase 1b/2 study, we will continue to advance Nana-val in this lead indication through regulatory approval as quickly as possible. We look forward to engaging with the FDA on a potential accelerated approval pathway midyear and sharing topline results from Stage 2 together with additional data from Stage 1 in the third quarter of 2024."

Key takeaways from the pivotal Phase 2 NAVAL-1 trial in patients with R/R EBV+ PTCL: Nana-val (nanatinostat in combination with valganciclovir) demonstrated greater efficacy than nanatinostat monotherapy and was generally well-tolerated. The median duration of response continues to mature.

Overview: A total of 20 patients with primarily Stage III-IV disease (who had received ≥1 [median of 2] prior systemic PTCL therapies) were randomized (1:1) to receive nanatinostat (20 mg orally once daily, 4 days/week) alone or as Nana-val in combination with valganciclovir (900 mg orally once daily, 7 days/week). Patients who did not respond to nanatinostat monotherapy after 6 weeks of treatment were offered the opportunity to cross over to receive Nana-val.
Efficacy was evaluated as of the February 7, 2024 data cutoff date.
In the Nana-val arm, the overall response rate (ORR) was 50% and the complete response rate (CRR) was 20% in the intent-to-treat (ITT) population (N=10); the ORR was 71% and the CRR was 29% in the efficacy-evaluable population (N=7).
In the nanatinostat monotherapy arm, the ORR and CRR were 10% and 0%, respectively, in the ITT population (N=10), and the ORR was 13% in the efficacy-evaluable population (N=8).
Five nanatinostat monotherapy patients crossed over to receive Nana-val, two of whom remain on Nana-val treatment with stable disease as of the data cutoff.
Safety was also evaluated as of the February 7, 2024 data cutoff date.
The most common treatment-related adverse events in both treatment arms were thrombocytopenia, anemia, fatigue, decreased appetite, nausea, diarrhea, and weight loss.
These adverse events were primarily mild to moderate in severity and generally manageable or reversible.
A copy of the data presentation is accessible under the "Events and Presentations" section of Viracta’s website at www.viracta.com.

About the NAVAL-1 Trial
NAVAL-1 (NCT05011058) is a global, multicenter, clinical trial of Nana-val in patients with relapsed or refractory (R/R) Epstein-Barr virus-positive (EBV+) lymphoma. This Phase 2 trial employs a Simon two-stage design where, in Stage 1, participants are enrolled into one of three indication cohorts based on EBV+ lymphoma subtype. If two objective responses are achieved within a lymphoma subtype in Stage 1 (n=10), then additional patients will be enrolled in Stage 2 for a total of 21 patients. EBV+ lymphoma subtypes demonstrating promising anti-tumor activity in Stage 2 may be further expanded following discussion with regulators to potentially support registration.

About Nana-val (Nanatinostat and Valganciclovir)
Nanatinostat is an orally available histone deacetylase (HDAC) inhibitor being developed by Viracta. Nanatinostat is selective for specific isoforms of Class I HDACs, which are key to inducing viral genes that are epigenetically silenced in Epstein-Barr virus (EBV)-associated malignancies. Nanatinostat is currently being investigated in combination with the antiviral agent valganciclovir as an all-oral combination therapy, Nana-val, in various subtypes of EBV-associated malignancies. Ongoing trials include a pivotal, global, multicenter, open-label, Phase 2 basket trial in multiple subtypes of relapsed or refractory (R/R) EBV+ lymphoma (NAVAL-1) as well as a multinational Phase 1b/2 clinical trial in patients with recurrent or metastatic (R/M) EBV+ NPC and other advanced EBV+ solid tumors.

About Peripheral T-Cell Lymphoma
T-cell lymphomas comprise a heterogeneous group of rare and aggressive malignancies, including peripheral T-cell lymphoma not otherwise specified (PTCL-NOS) and angioimmunoblastic T-cell lymphoma (AITL). There are approximately 5,600 newly diagnosed T-cell lymphoma patients and approximately 2,600 newly diagnosed PTCL-NOS and AITL patients in the U.S. annually. Approximately 70% of these patients are either refractory to first-line therapy, or eventually experience relapse of their disease. Clinical trials are currently recommended for all lines of PTCL therapy, and most patients with R/R PTCL have poor outcomes, with median progression-free survival and median overall survival times reported to be 3.7 and 6.5 months, respectively. Approximately 40% to 65% of PTCL is associated with EBV, the incidence of EBV+ PTCL varies by geography, and reported outcomes for patients with EBV+ PTCL are inferior to those whose disease is EBV-negative. There is no approved targeted treatment specific for EBV+ PTCL, and therefore this represents a high unmet medical need.

About EBV-Associated Cancers
Approximately 90% of the world’s adult population is infected with EBV. Infections are commonly asymptomatic or associated with mononucleosis. Following infection, the virus remains latent in a small subset of cells for the duration of the patient’s life. Cells containing latent virus are increasingly susceptible to malignant transformation. Patients who are immunocompromised are at an increased risk of developing EBV-positive (EBV+) lymphomas. EBV is estimated to be associated with approximately 2% of the global cancer burden including lymphoma, nasopharyngeal carcinoma (NPC), and gastric cancer.

On April 15, 2024 UroGen Pharma Ltd. (Nasdaq: URGN), a biotech company dedicated to developing and commercializing novel solutions that treat urothelial and specialty cancers, reported the U.S. Food and Drug Administration (FDA) accepted the Company’s Investigational New Drug (IND) application for UGN-103, a next-generation novel mitomycin-based formulation for low-grade intermediate-risk non-muscle invasive bladder cancer (LG-IR-NMIBC) (Press release, UroGen Pharma, APR 15, 2024, View Source [SID1234642074]).

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The UGN-103 formulation uses UroGen’s RTGel platform technology, a proprietary sustained-release, reverse-thermal hydrogel that can improve the therapeutic profiles of existing drugs. UGN-103 is anticipated to provide several advantages related to production, cost, supply, and product convenience if approved. UroGen plans to initiate a Phase 3 study in 2024 to explore the safety and efficacy of UGN-103 for the treatment of LG-IR-NMIBC, a highly recurrent disease.

"We are delighted by the FDA’s acceptance of our IND for UGN-103, marking a significant step forward in our mission," said Liz Barrett, President and Chief Executive Officer of UroGen. "We eagerly anticipate commencing a clinical trial with UGN-103 this year, as we strive to continually advance and develop treatments for patients with high unmet need."

UGN-103 is planned to follow the anticipated FDA approval and launch of UGN-102 (mitomycin) for intravesical solution for LG-IR-NMIBC. UroGen intends to complete the rolling new drug application (NDA) submission for UGN-102 in September 2024, with a potential FDA decision as early as the first quarter of 2025 if priority review is granted by FDA.

About UGN-103

UGN-103 (mitomycin) for intravesical solution is an innovative drug formulation of mitomycin being developed for the treatment of LG-IR-NMIBC. UroGen plans to initiate a Phase 3 study to explore the safety and efficacy of UGN-103 in 2024. Anticipated advantages of UGN-103 include a new 80 mg mitomycin dosage strength that may considerably shorten the manufacturing process, simplify the reconstitution procedure, and potentially extend intellectual property protection until as late as December 2041. UGN-103 will utilize UroGen’s proprietary RTGel technology, a sustained release, hydrogel-based formulation designed to enable longer exposure of bladder tissue to mitomycin, thereby enabling the treatment of tumors by non-surgical means.

About UGN-102

UGN-102 (mitomycin) for intravesical solution is an innovative drug formulation of mitomycin, currently in Phase 3 development for the treatment of LG-IR-NMIBC. Utilizing UroGen’s proprietary RTGel technology, a sustained release, hydrogel-based formulation, UGN-102 is designed to enable longer exposure of bladder tissue to mitomycin, thereby enabling the treatment of tumors by non-surgical means. UGN-102 is delivered to patients using a standard urinary catheter in an outpatient setting. Assuming positive findings from the durability of response endpoint from the ENVISION Phase 3 study, UroGen anticipates submitting an NDA for UGN-102 in September 2024 and a potential FDA decision as early as the first quarter of 2025.

On April 15, 2024 RenovoRx, Inc. ("RenovoRx" or the "Company") (Nasdaq: RNXT), a clinical-stage biopharmaceutical company developing novel precision oncology therapies based on a local drug-delivery platform, reported the closing of its previously announced private placement of approximately $11.1 million in gross proceeds (Press release, Renovorx, APR 15, 2024, View Source [SID1234642073]).

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Shaun Bagai, Chief Executive Officer of RenovoRx, stated, "We believe our recent financing achievements mark a critical milestone for RenovoRx. Our April and January 2024 private placements, in which we raised $17.2 million in total gross proceeds, strengthen our balance sheet and energize our drive towards knowable value creation events over the next two years. These include: first, the continuation of our pivotal Phase III TIGeR-PaC clinical trial in locally advanced pancreatic cancer towards a second interim readout and ultimate completion; second, the expansion of our TAMP clinical development pipeline into additional cancer indications; and third, our ongoing exploration of new commercial business development opportunities with our therapeutic technologies. These investments in our Company validate our vision to build a better way to treat difficult-to-access cancers for not only oncology patients, but their clinicians and loved ones, all as we seek to drive value for our stockholders."

Mr. Bagai added, "We are proud of our achievements to date and grateful for the support of our existing and new investors. With this support, our team will continue its commitment to improving patients’ lives and lifespans by delivering therapies that have the potential to revolutionize the current paradigm of cancer care."

The TIGeR-PaC study is an ongoing randomized multi-center study in locally advanced pancreatic cancer (LAPC) using the Company’s patented Trans-Arterial Micro-Perfusion (TAMP) platform to evaluate the Company’s first product candidate, RenovoGem, a novel oncology drug-device combination product. The study is comparing treatment with TAMP to the current standard of care (systemic intravenous chemotherapy). RenovoRx expects that the second interim analysis for this study will be triggered by the 52nd event in the trial, which is estimated to occur in late 2024.

Newbridge Securities Corporation acted as sole placement agent for the transaction. Ellenoff Grossman & Schole LLP acted as legal counsel to RenovoRx, and McGuireWoods LLP acted as legal counsel to Newbridge Securities Corporation.

On April 15, 2024 Outlook Therapeutics, Inc. (Nasdaq: OTLK), a biopharmaceutical company working to achieve the first approval for an ophthalmic formulation of bevacizumab for the treatment of retinal diseases in the US and the EU, reported that it has closed its previously announced private placement with Syntone Ventures, LLC, an existing stockholder, for upfront gross proceeds of approximately $5.0 million from the issuance and sale of shares of the Company’s common stock and accompanying warrants, before deducting offering expenses (Press release, Outlook Therapeutics, APR 15, 2024, View Source [SID1234642072]). In addition, Outlook Therapeutics has the potential to receive additional gross proceeds of up to $8 million upon the full cash exercise of the warrants issued in the private placement, before deducting offering expenses.

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About the Private Placement

Pursuant to the securities purchase agreement entered into on January 24, 2024, Outlook Therapeutics issued to Syntone an aggregate of 714,286 shares of common stock and accompanying warrants to purchase an aggregate of 1,071,429 shares of common stock, at a price of $7.00 per share and accompanying warrant to purchase one and one-half shares of common stock. The warrants have an exercise price of $7.70 per share and are exercisable only for cash until their expiration on the fifth anniversary of the issuance date. The warrants include a feature that allows Outlook Therapeutics to require Syntone to cash exercise the warrants if certain stock price and milestone conditions are met.

All of the securities in the private placement were offered by the Company.

Outlook Therapeutics intends to use the net proceeds from the private placement to fund its ONS-5010 clinical development programs, including the ongoing NORSE EIGHT clinical trial, and for working capital and other general corporate purposes.

As previously disclosed, Outlook Therapeutics also entered into, and received proceeds from, a securities purchase agreement with Great Point Partners, LLC, GMS Ventures, and other investors to purchase $60 million in shares of common stock and warrants on substantially the same terms as the private placement.

The offer and sale of the foregoing securities were made by Outlook Therapeutics in a private placement under Section 4(a)(2) of the Securities Act of 1933, as amended (the "Act"), and/or Regulation D promulgated thereunder, and such securities have not been registered under the Act or applicable state securities laws. Accordingly, such securities may not be offered or sold in the United States except pursuant to an effective registration statement or an applicable exemption from the registration requirements of the Act and such applicable state securities laws. Outlook Therapeutics has agreed to file a resale registration statement with the U.S. Securities and Exchange Commission for purposes of registering the resale of the common stock issued or issuable in connection with the private placement.

This press release shall not constitute an offer to sell or a solicitation of an offer to buy any of the securities described herein 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.

About ONS-5010 / LYTENAVA (bevacizumab-vikg, bevacizumab gamma)

ONS-5010/LYTENAVA is an investigational ophthalmic formulation of bevacizumab under development as an intravitreal injection for the treatment of wet AMD and other retinal diseases. Because no FDA or European Commission approved ophthalmic formulations of bevacizumab are available currently, clinicians wishing to treat retinal patients with bevacizumab have had to use repackaged IV bevacizumab provided by compounding pharmacies—products that have known risks of contamination and inconsistent potency and availability. If approved, ONS-5010/LYTENAVA would provide an approved option for physicians to treat wet AMD.

Bevacizumab-vikg/bevacizumab gamma is a recombinant humanized monoclonal antibody (mAb) that selectively binds with high affinity to all isoforms of human vascular endothelial growth factor (VEGF) and neutralizes VEGF’s biologic activity through a steric blocking of the binding of VEGF to its receptors Flt-1 (VEGFR-1) and KDR (VEGFR-2) on the surface of endothelial cells. Following intravitreal injection, the binding of bevacizumab-vikg to VEGF prevents the interaction of VEGF with its receptors on the surface of endothelial cells, reducing endothelial cell proliferation, vascular leakage, and new blood vessel formation in the retina.

On April 15, 2024 ORIC Pharmaceuticals, Inc. (Nasdaq: ORIC), a clinical stage oncology company focused on developing treatments that address mechanisms of therapeutic resistance, reported the completion of the dose escalation portion of the Phase 1b trial of ORIC-114 in patients with advanced solid tumors with EGFR and HER2 exon 20 alterations or HER2 amplifications (Press release, ORIC Pharmaceuticals, APR 15, 2024, View Source [SID1234642071]). Based upon these data, ORIC selected the two provisional recommended Phase 2 dose (RP2D) levels of ORIC-114 at 80 mg and 120 mg QD, which are being further evaluated in three dose expansion cohorts for dose optimization and final RP2D selection. These expansion cohorts have now been initiated in patients with non-small cell lung cancer (NSCLC) with EGFR exon 20 (EGFR exon 20 inhibitor naïve), HER2 exon 20, or EGFR atypical mutations. The company also announced the initiation of an extension cohort for the treatment of patients with first-line, treatment-naïve EGFR exon 20 NSCLC.

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"Following the positive dose escalation data reported at ESMO (Free ESMO Whitepaper) 2023, we are excited to announce the advancement of ORIC-114 into Phase 1b dose expansion," said Pratik Multani, M.D., chief medical officer of ORIC. "Encouraging findings from the Phase 1b dose escalation phase of the trial demonstrated a potential best-in-class profile for ORIC-114, with notable systemic responses and CNS responses, as well as a favorable safety profile, in heavily pre-treated patients. Based on these results, we have identified the two dose levels that we are now advancing into Phase 1b expansion cohorts to determine the final RP2D for further development, including potential registrational cohorts. At the request of many of our investigators and because of the lack of other CNS-active agents against EGFR exon 20, we are also extending our trial to include a cohort evaluating first-line, treatment-naïve NSCLC. We are hopeful that the expansion portion of the trial will validate and build upon the encouraging efficacy seen in the dose escalation, and plan to report results in the first half of 2025."

The Phase 1b dose escalation part of the trial evaluated ORIC-114 in patients with advanced solid tumors with EGFR and HER2 exon 20 alterations or HER2 amplifications. Patients previously treated with an exon 20 targeted agent were eligible, including patients with CNS metastases that were either treated or untreated but asymptomatic. Nearly all other clinical trials with EGFR exon 20 inhibitors severely restricted the eligible patient population and excluded patients with active or untreated brain metastases and patients previously treated with an EGFR exon 20 inhibitor. The primary objectives were to determine the provisional RP2D, and additional objectives included characterization of the safety, tolerability, pharmacokinetic, and preliminary antitumor activity.

The Phase 1b expansion portion of the trial will evaluate the safety and efficacy of ORIC-114 at the provisional RP2D levels of 80 mg and 120 mg QD in patients with mutated NSCLC, including EGFR exon 20 (EGFR exon 20 inhibitor naïve), HER2 exon 20, and EGFR atypical mutations. The primary objectives are to determine the RP2D, and additional objectives include assessment of efficacy in terms of objective response rate, duration of response and progression-free survival, including intracranial activity, as well as further characterization of the safety profile of ORIC-114.

About ORIC-114
ORIC-114 is a highly selective, brain penetrant, orally bioavailable, irreversible inhibitor designed to selectively target EGFR and HER2 with high potency against exon 20 insertion mutations, making it a promising therapeutic candidate to address the unmet medical need of having both meaningful systemic as well as CNS antitumor activity.