On May 15, 2023 Outlook Therapeutics, Inc. (Nasdaq: OTLK), a biopharmaceutical company working to develop and launch the first FDA-approved ophthalmic formulation of bevacizumab for use in retinal indications, reported recent corporate highlights and financial results for its fiscal second quarter ended March 31, 2023 (Press release, Outlook Therapeutics, MAY 15, 2023, View Source [SID1234631740]).

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"We continue to make significant progress in our pre-launch activities as we approach our PDUFA goal date set for August 29, 2023, just three short months away. These initiatives are focused on positioning Outlook Therapeutics as an upcoming leader in the anti-VEGF space by meeting FDA requirements for an ophthalmic approval. The ONS-5010 Biologics License Application (BLA) was submitted and accepted for filing by the FDA as a 351(a) stand-alone BLA. We believe ONS-5010, if approved, has the potential to be the standard of care in the retinal anti-VEGF space and look forward to potentially bringing to market the first FDA-approved ophthalmic formulation of bevacizumab," commented Russell Trenary, President and Chief Executive Officer of Outlook Therapeutics.

Upcoming Anticipated Milestones

Continued progress with ongoing pre-launch commercial preparations in anticipation of potential approval for ONS-5010 in 2023;
PDUFA goal date of August 29, 2023;
Continued evaluation of ONS-5010 in a pre-filled syringe in the NORSE SEVEN clinical trial; and
Estimated decision date from the EMA’s CHMP on the Company’s submitted MAA in the EU for ONS-5010 expected in early 2024.
Commercial Planning Underway to Support Potential Approval of the First Ophthalmic Formulation of Bevacizumab for Use in Retinal Indications

According to GlobalData, the use of unapproved repackaged IV bevacizumab from compounding pharmacies is estimated to account for approximately 50% of all wet AMD injections in the United States each year. This represents approximately 3.5 million injections of off-label, repackaged bevacizumab each year in the United States alone. Globally, the nine major markets account for an estimated $13.1 billion market for anti-VEGF drugs to treat retina diseases.

Because patients, physicians and payors rely heavily on bevacizumab as an important option for treating wet AMD, ONS-5010 has been developed to address the potential potency and safety issues that have been reported to be associated with using off-label, repackaged bevacizumab from compounding pharmacies, including:

As reported in a study published in JAMA, 81% of all tested syringes of repackaged bevacizumab received from compounding pharmacies contained suboptimal protein concentrations, which could result in lower clinical efficacy.
Non-standard materials used to transfer and hold repackaged bevacizumab can potentially add particulates to non-ophthalmic-designed bevacizumab, which in turn may fail to meet the standards FDA requires for ophthalmic compounds.
In August 2022, Outlook Therapeutics submitted a PHSA 351(a) BLA for ONS-5010 as a standalone biologic to potentially become the only approved ophthalmic formulation of bevacizumab. ONS-5010, if approved, cannot qualify as a biosimilar because the PHSA requires a biosimilar to have the same "conditions of use" (e.g., indications) as a reference product. AVASTIN, the currently marketed non-ophthalmic formulation of bevacizumab, is not approved by FDA for the treatment of wet AMD or other retinal diseases.

In the NORSE TWO Phase 3 clinical trial, which compared ONS-5010 (dosed monthly) with LUCENTIS (using the PIER dosing regimen), ONS-5010 showed significantly higher results in improving BCVA by ≥ 15 letters from baseline at 11 months (41.7% compared to 23.1% in LUCENTIS group, p = 0.0052). Patients receiving ONS-5010 also demonstrated statistically significant mean change in BCVA of 11.2 letters compared to 5.8 letters in the control arm (p = 0.0043). Additionally, the majority of ONS-5010 subjects maintained or gained BCVA during the study (defined as change from baseline in BCVA ≥ 0), with at least 80% of ONS-5010 subjects maintaining BCVA each month. Safety evaluations revealed similar safety profiles of ONS-5010 and the comparator LUCENTIS. In fact, only one serious ocular adverse event occurred in the ONS-5010 arm (increase in intraocular pressure) in 1100 injections.

If approved, ONS-5010 / LYTENAVA (bevacizumab-vikg) will be the first ophthalmic formulation of bevacizumab, not a biosimilar.

ONS-5010 / LYTENAVA (bevacizumab-vikg) Pre-Launch Preparations Proceeding as Planned

In anticipation of potential FDA marketing approval in 2023, Outlook Therapeutics has begun commercial launch planning, including best-in-class partnerships with FUJIFILM Diosynth Biotechnologies for drug substance, and with drug product manufacturer Aji Bio-pharma Services for the finished drug product.

Outlook Therapeutics is actively building out its sales and commercial team, and in September, 2022 Outlook Therapeutics entered into a strategic partnership with AmerisourceBergen in preparation for the anticipated commercial launch in the United States of ONS-5010. As Outlook Therapeutics moves toward a potential launch in the United States, AmerisourceBergen’s commercialization support will expand to include additional services. Through the agreement with AmerisourceBergen, Outlook Therapeutics expects to significantly increase market access and efficient distribution of ONS-5010, if approved by the FDA. Moreover, working with AmerisourceBergen will help to provide Outlook Therapeutics with an accelerated pathway to deliver a high-quality customer experience to retina specialists. To bring ONS-5010 to market in a way that benefits all stakeholders – patients, clinicians, and payors – Outlook Therapeutics has also been in collaborative discussions with payors and the retina community.

Outlook Therapeutics also submitted a Marketing Authorization Application (MAA) in Europe, which was validated for review in December 2022. The formal review process of the MAA by the EMA’s Committee for Medicinal Products for Human Use (CHMP) is underway with an estimated decision date expected in early 2024. In addition to pursuing potential strategic partnering opportunities in the EU and other regions, such as the current partnership with Syntone Biopharma JV in China, Outlook Therapeutics is also exploring an expanded relationship with AmerisourceBergen to support the launch of ONS-5010 in international markets. AmerisourceBergen increased its global distribution capabilities in 2021 with the acquisition of PharmaLex and Alliance Healthcare, leading wholesalers and specialized service provider of healthcare products in Europe.

In addition to the clinical development program evaluating ONS-5010 for wet AMD, Outlook Therapeutics has received agreements from the FDA on three Special Protocol Assessments (SPAs) for three additional registration clinical trials. These SPAs cover the protocols for a planned registration clinical trial evaluating ONS-5010 to treat branch retinal vein occlusion (BRVO), NORSE FOUR, and two planned registration clinical trials evaluating the drug candidate for the treatment of diabetic macular edema (DME), NORSE FIVE and NORSE SIX.

Financial Highlights for the Fiscal Second Quarter Ended March 31, 2023

For the fiscal second quarter ended March 31, 2023, Outlook Therapeutics reported a net loss attributable to common stockholders of $6.7 million, or $0.03 per basic and diluted share, compared to a net loss attributable to common stockholders of $19.7 million, or $0.09 per basic and diluted share, for the same period last year.

As of March 31, 2023, Outlook Therapeutics has cash and cash equivalents of $43.7 million, which is expected to be sufficient to fund its operations through the anticipated approval of the BLA for ONS-5010 in the third calendar quarter of 2023, and potentially through the fourth calendar quarter of 2023.

About ONS-5010 / LYTENAVA (bevacizumab-vikg)

ONS-5010 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 currently approved ophthalmic formulations of bevacizumab are available, clinicians wishing to treat retinal patients with bevacizumab have had to use unapproved repackaged IV bevacizumab provided by compounding pharmacies, products that have known risks of contamination and inconsistent potency and availability. If approved, ONS-5010 can replace the need to use unapproved repackaged oncologic IV bevacizumab from compounding pharmacies for the treatment of wet AMD.

Bevacizumab-vikg 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 May 15, 2023 Onconova Therapeutics, Inc. (NASDAQ: ONTX), ("Onconova"), a clinical-stage biopharmaceutical company focused on discovering and developing novel products for patients with cancer, reported financial results for the three months ended March 31, 2023, and provided a business update (Press release, Onconova, MAY 15, 2023, View Source [SID1234631739]).

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Highlights for the first quarter of 2023 and recent weeks include:

· The first participant was dosed in the Phase 1/2a trial of narazaciclib combined with letrozole in recurrent metastatic low-grade endometrioid endometrial cancer (LGEEC). The trial remains on track for a preliminary data readout from its Phase 1 portion in the fourth quarter of this year.

· Safety data from the Phase 1 solid tumor trial evaluating a continuous daily dosing schedule of narazaciclib continue to be encouraging with the maximum tolerated dose awaiting confirmation. The trial has enrolled patients in its sixth dose escalation cohort, which evaluates a 240 mg oral dose of narazaciclib.

· Two posters presented at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting featured the results of preclinical studies of narazaciclib. Data showed that, in addition to inhibiting kinases such as CDK 4 and CDK 6, narazaciclib treatment led to the degradation of other kinases not targeted by the FDA-approved CDK 4/6 inhibitor palbociclib. These kinases included BUB1, the overexpression of which was shown to be associated with poor prognosis in breast cancer and uterine corpus endometrial carcinomas. In addition, data presented showed that narazaciclib’s activity in several preclinical cancer models compared favorably to that of FDA-approved CDK 4/6 inhibitors.

· The second of two evaluable participants in the investigator-sponsored Phase 2 program evaluating rigosertib monotherapy in advanced squamous cell carcinoma complicating recessive dystrophic epidermolysis bullosa (RDEB-associated SCC) achieved a complete clinical response of all cancerous skin lesions following four treatment cycles of oral rigosertib. Thus, both patients evaluable for response achieved complete cutaneous remissions (CCR). This data and the rational for the study of rigosertib in RDEB-SCC was presented at the recent meeting of the Society of Investigative Dermatology Meeting in Osaka, Japan. Onconova has requested a Type B Meeting to review these initial data with the U.S. Food and Drug Administration (FDA), with the goal of identifying the optimal regulatory path for rigosertib in RDEB-associated SCC. Onconova expects to provide an update on the Type B meeting after it has received written feedback from the agency.

· Rigosertib’s additional investigator-sponsored trials continue to progress. A Phase 2 trial of rigosertib combined with Merck’s anti-PD-1 therapy KEYTRYDA (pembrolizumab) in checkpoint inhibitor refractory melanoma recently opened for enrollment. The Phase 1/2a trial of rigosertib in combination with Bristol Meyer Squibb’s OPDIVO (nivolumab) in KRAS-mutated non-small cell lung cancer (NSCLC) is ongoing. Based on previously reported data that showed an encouraging signal of efficacy and that the studied doublet was well tolerated. The NSCLC trial protocol has been amended to add cohorts evaluating increasing doses of rigosertib in combination with the standard dose of nivolumab. Data from these additional cohorts are expected alongside updated data from the trial’s earlier cohorts in 2023.

· Onconova recently entered into a collaboration agreement with Pangea Biomed. The collaboration will leverage Pangea Biomed’s proprietary algorithmic platform, ENLIGHT, with the goal of identifying biomarkers of response to rigosertib. Onconova retains all rights to rigosertib and will own intellectual property that may result from the research collaboration.

· Preclinical data characterizing rigosertib’s multi-faceted mechanism of action were recently featured in a poster presentation at the AACR (Free AACR Whitepaper) Targeting RAS Conference.

Management Commentary

"Recent progress has us approaching important clinical and regulatory milestones expected later this year," said Steven M. Fruchtman, M.D., President and Chief Executive Officer of Onconova. "We recently dosed the first participant in our Phase 1/2a trial of narazaciclib plus letrozole in recurrent metastatic LGEEC. This trial is supported by prior clinical data providing proof-of-concept for the studied doublet’s mechanism of action, as well as preclinical and Phase 1 results that suggest narazaciclib can overcome the shortcomings of the off-label agents current combined with letrozole to treat this indication. Collectively, these data fuel our enthusiasm for the program as we advance towards a preliminary data readout expected in the fourth quarter."

Dr. Fruchtman continued, "In rigosertib’s RDEB-associated SCC program, we have requested a Type B meeting to discuss our encouraging clinical data with the FDA and expect to provide an important regulatory update following the meeting. Though from a small number of patients, these data have far exceeded our expectations, with both of the program’s participants achieving durable, complete clinical responses of all cancerous skin lesions on rigosertib monotherapy. Given the strength of these data, the ultra-rare nature of RDEB-associated SCC, and the stark limitations of currently available therapies, we are committed to working with the agency to determine the best, most expeditious path towards a potential approval."

First Quarter Financial Results

Cash and cash equivalents as of March 31, 2023 were $34.2 million compared with $38.8 million as of December 31, 2022. The company believes that its cash and cash equivalents will be sufficient to fund ongoing clinical trials and business operations into the first quarter of 2024.

Research and development expenses were $4.1 million for the first quarter of 2023, compared with $2.0 million for the first quarter of 2022.

General and administrative expenses were $2.1 million for the first quarter of 2023, compared with $2.2 million for the first quarter of 2022.

Net loss for the first quarter of 2023 was $5.8 million, or $0.28 per share on 20.9 million weighted shares outstanding, compared with a net loss of $4.1 million, or $0.20 per share for the first quarter of 2022 on 20.9 million weighted shares outstanding.

Conference Call and Webcast

Onconova will host an investment community conference call beginning at 4:30 p.m. Eastern Time, during which management will discuss financial results for the first quarter of 2023, provide a business update, and answer questions. Interested parties can participate by dialing (800) 715-9871 (domestic callers) or (646) 307-1963 (international callers) and using conference ID 9090989.

A live webcast of the conference call will be available in the Investors & Media section of the Company’s website at www.onconova.com. A replay of the webcast will be available on the Onconova website for 90 days following the call.

On May 15, 2023 Nuvectis Pharma, Inc. (NASDAQ: NVCT) ("Nuvectis" or the "Company"), a clinical-stage biopharmaceutical company focused on the development of innovative precision medicines for the treatment of serious conditions of unmet medical need in oncology, reported that the U.S. Food and Drug Administration ("FDA") cleared the Company’s Investigational New Drug Application ("IND") for NXP900, which includes the Phase 1 clinical trial protocol (Press release, Nuvectis Pharma, MAY 15, 2023, View Source [SID1234631738]).

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"The IND clearance by the FDA is a significant milestone for the NXP900 development program and for our overall corporate strategy, further demonstrating our ability to execute our business plan," said Ron Bentsur, Chairman and Chief Executive Officer of Nuvectis. Mr. Bentsur continued, "Nuvectis now has two precision oncology, clinical-stage drug candidates, each with several potential opportunities in cancers that represent serious conditions of unmet medical need. We believe that NXP900 presents a unique opportunity due to its differentiated mechanism of action and pharmacologic attributes, and we are excited to start the clinical program to unlock its therapeutic potential."

About NXP900

Nuvectis licensed exclusive world-wide rights to NXP900, a novel inhibitor of the SRC family of kinases ("SFKs") with low nanomolar potency against YES1 and SRC, from the University of Edinburgh in Scotland. Over activation of SFKs occurs frequently in tumor tissues and they are central mediators in multiple oncogenic signaling pathways. YES1, a key member of the SFKs, enhances the phosphorylation, nuclear localization and oncogenic activity of YAP1, a key Hippo pathway effector. In preclinical studies, NXP900 demonstrated robust single agent antitumor activity in several in vivo xenograft models, including in squamous cell cancers such as cervical, head and neck and esophageal carcinomas in which Hippo pathway mutations and copy number abnormalities are prevalent. In addition, NXP900 in combination with osimertinib (the active ingredient in TAGRISSO) in vitro and with enzalutamide (the active ingredient in Xtandi) in vivo demonstrated the potential ability to reverse acquired resistance to these drugs in non-small cell lung cancer and metastatic castration-resistant prostate cancer, respectively.

On May 15, 2023 Nusano, Inc., a company reshaping the production of cancer-fighting radioisotopes, and PharmaLogic, a world-class contract development and manufacturing organization (CDMO) specializing in radiopharmaceuticals, reported that the two organizations will collaborate to advance the development of radiopharmaceuticals for diagnostic and therapeutic applications (Press release, Nusano, MAY 15, 2023, View Source [SID1234631737]).

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"PharmaLogic and Nusano share a vision for improving cancer outcomes by empowering the development of next generation radiopharmaceuticals," said Chris Lowe, CEO of Nusano. "Our facilities’ close proximity in the greater Salt Lake area creates natural opportunities for collaboration and early-stage research we believe will be advantageous to our joint customer base."

Opening the first quarter of 2025, Nusano’s breakthrough production facility in West Valley City, Utah will be capable of generating multiple medical isotopes simultaneously and in large quantities to support patient care and therapeutic development.

PharmaLogic Utah will be opening in Salt Lake City in the latter half of 2023, expanding its CDMO and radiopharmaceutical manufacturing capabilities in the mountain west region of the United States. PharmaLogic, in addition to their established radiopharmacy business, has focused on the growth of their cyclotron network and footprint in the CDMO space to increase access to the latest radiopharmaceutical technology for patients across the United States. The facility in Salt Lake City is one of the latest additions to the organization’s portfolio.

"Radioisotope supply chain stability is critical to ensuring diagnostics and treatments reach patients when they are needed," said Scott Holbrook, Chief Strategy Officer and General Manager for PharmaLogic. "Nusano’s facility will bring undersupplied and rare radioisotopes online, complementing PharmaLogic’s commitment to providing quality and predictability for our customers. We look forward to working together to accelerate new and emerging cancer diagnostics and treatments."

On May 15, 2023 NUCLIDIUM and PharmaLogic Holdings reported that they have entered into a strategic collaboration agreement for the production and clinical supply of 61Cu in the United States to accelerate the development of NUCLIDIUM’s theranostic pipeline (Press release, NUCLIDIUM, MAY 15, 2023, View Source [SID1234631736]). By combining copper radiometals with highly specific cancer-targeting molecules, NUCLIDIUM’s theranostic approach aims to offer innovative diagnostic and therapeutic treatments for patients suffering from a range of solid tumours. The partnership with PharmaLogic will provide NUCLIDIUM with a sustainable supply of 61Cu in the United States both for its planned clinical trials as well as future commercialized products. NUCLIDIUM has developed a proprietary production process for high-quality 61Cu, a novel diagnostic radioisotope that offers unique properties for safe, economical, and highly efficient diagnostics to improve cancer-staging and subsequent treatment decisions

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Under the terms of the agreement, NUCLIDIUM will provide PharmaLogic with the scientific know-how, proprietary technology, and raw material to enable PharmaLogic to safely and accurately produce high-quality 61Cu-radionuclides and radiopharmaceuticals in their manufacturing facilities throughout the US. The first product batch is planned to be manufactured in 2023 at PharmaLogic’s location in Los Angeles, California. NUCLIDIUM will retain all rights to its proprietary platforms and technologies. Financial details of the collaboration were not disclosed.

"PharmaLogic is a well-established and highly experienced CDMO with a robust manufacturing network to supply diagnostic and therapeutic radiopharmaceuticals across North America. Their commitment to work with us emphasises the opportunity represented by our innovative theranostic approach. With this agreement, we are further ensuring the sustainable supply of copper-based isotopes to advance our programs towards the clinic, specifically two of our pipeline candidates which are targeted to reach the clinic this year," said Leila Jaafar, PhD, CEO and Co-Founder of NUCLIDIUM.

"Targeted radiotheranostics offer a novel, personalized solution for cancer patients with the potential to become an integral part of cancer diagnosis and treatment. NUCLIDIUM’s copper-based platform has the ability to bring us closer to this vision, and I look forward to working with this highly skilled team to advance radiopharmaceutical products jointly and serve cancer patients in North America by reliably providing them with clinically relevant medical options," said Steve Chilinski, CEO of PharmaLogic.

61Cu radionuclides are uniquely positioned to transform the diagnosis of particularly hard-to-diagnose tumours. They can be produced through easily accessible source material and, in contrast to other available diagnostics, have a half-life that enables delayed imaging to find even the smallest metastasis. In addition, 61Cu decays into a stable isotope which keeps the radiation burden for the patient low and reduces waste at the treatment sites. NUCLIDIUM’s easy-to-apply proprietary production process allows for fast and easy integration into an installed cyclotron and existing supply networks for PET-FDG, making it a safe and economical solution for producing radiopharmaceuticals.

About NUCLIDIUM’s Copper-based Platform
Nuclidium’s copper-based platform enables an easy adjustment of each product candidate from a diagnostic to a therapeutic by simply exchanging 61Cu with 67Cu. Through this approach, both product candidates are biodistributed in the body identically, allowing for exact dosimetry for each patient. This seamless "diagnostic to therapeutic" approach offers the potential for more personalised, efficacious, and safe patient care compared to other radiopharmaceuticals that use different radioisotopes and/or targeting molecules for diagnosis and treatment. Importantly, the easy-to-apply proprietary production process and half-live properties of the copper radioisotopes contribute to a superior radiotheranostic product with broad availability.