On October 11, 2021 Geron Corporation (Nasdaq: GERN), a late-stage biopharmaceutical company focused on the development and commercialization of treatments for hematologic malignancies, reported the publication in the Annals of Hematology of a paper entitled "Favorable Overall Survival with Imetelstat in Relapsed/Refractory Myelofibrosis Patients Compared with Real World Data," which details statistical analyses comparing data from the Company’s IMbark Phase 2 clinical trial to closely matched Real World Data (RWD) (Press release, Geron, OCT 11, 2021, View Source [SID1234591065]).

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"Across the multiple analyses presented in the publication, the median overall survival for imetelstat-treated patients in our IMbark Phase 2 clinical trial was consistently more than double than the median overall survival for patients treated with best available therapy (BAT) from RWD. For the imetelstat-treated patients, the median overall survival (OS) was approximately 30 months in comparison to approximately 12 months for BAT-treated patients from RWD," said Aleksandra Rizo, M.D., Ph.D., Geron’s Chief Medical Officer. "We are pleased with the publication of this important work as these analyses provide us further confidence in the use of OS as the primary endpoint for our ongoing confirmatory IMpactMF Phase 3 trial."

The paper describes several statistical adjustment methods and multiple sensitivity analyses to improve comparability of the data set from the Company’s IMbark Phase 2 trial and RWD to mimic the effect of a randomized trial. The authors note consistency in the hazard ratios and statistical significance observed across the multiple analyses, which suggests a survival benefit associated with imetelstat treatment of MF patients after ruxolitinib failure. While acknowledging the limitations of RWD analyses, the authors conclude that the results of these analyses warrant further prospective evaluation of imetelstat in a Phase 3 setting with OS as a primary endpoint.

"The RWD used in this paper was collected from patients treated with BAT at the Moffitt Cancer Center after they had discontinued treatment from ruxolitinib, a JAK inhibitor," said Rami Komrokji, M.D., Vice Chair, Department of Malignant Hematology at Moffitt Cancer Center. "There is an urgent and unmet need for treatment options with a novel mechanism of action for MF patients who are relapsed/refractory to JAK inhibitors. The reported favorable OS with imetelstat treatment in this as well as in prior publications in this very poor prognosis MF patient population differentiates imetelstat from other therapeutic agents in development for MF today. We are excited to participate in Geron’s ongoing IMpactMF clinical trial to confirm these data."

The publication is available online at View Source

Ongoing IMpactMF Phase 3 Clinical Trial

IMpactMF is an open label, randomized, controlled Phase 3 clinical trial with registrational intent. The trial is designed to enroll approximately 320 patients with Intermediate-2 or High-risk myelofibrosis who are refractory to prior treatment with a JAK inhibitor, also referred to as refractory MF. Patients will be randomized to receive either imetelstat or best available therapy. The primary endpoint is overall survival (OS). Key secondary endpoints include symptom response, spleen response, progression free survival, complete response, partial response, clinical improvement, duration of response, safety, pharmacokinetics, and patient reported outcomes.

IMpactMF is currently enrolling patients. For further information about IMpactMF, including enrollment criteria, locations and current status, visit ClinicalTrials.gov/NCT04576156.

About Myelofibrosis (MF)

Myelofibrosis, a type of myeloproliferative neoplasm, is a chronic blood cancer in which abnormal or malignant precursor cells in the bone marrow proliferate rapidly, causing scar tissue, or fibrosis, to form. People with MF may have abnormally low or high numbers of circulating red blood cells, white blood cells or platelets, and abnormally high numbers of immature cells in the blood or bone marrow. MF patients can also suffer from debilitating constitutional symptoms, such as drenching night sweats, fatigue, severe itching, or pruritus, abdominal pain, fever and bone pain.

Approximately 70% of MF patients are classified as having Intermediate-2 or High-risk disease, as defined by the Dynamic International Prognostic Scoring System Plus. There are more than 35,000 patients worldwide and more than 13,000 patients in the U.S. living with Intermediate-2 or High-risk MF. The only drug therapies approved for treating these MF patients are JAK inhibitors. Currently, MF patients who fail or no longer respond to JAK inhibitor treatment have no or limited options, resulting in shortened median overall survival.

About Imetelstat

Imetelstat is a novel, first-in-class telomerase inhibitor exclusively owned by Geron and being developed in myeloid hematologic malignancies. Data from Phase 2 clinical trials provide strong evidence that imetelstat targets telomerase to inhibit the uncontrolled proliferation of malignant stem and progenitor cells in myeloid hematologic malignancies resulting in malignant cell apoptosis and potential disease-modifying activity. Imetelstat has been granted Fast Track designation by the United States Food and Drug Administration for both the treatment of patients with non-del(5q) lower risk MDS who are refractory or resistant to an erythropoiesis-stimulating agent (ESA) and for patients with Intermediate-2 or High-risk MF whose disease has relapsed after or is refractory to janus associated kinase (JAK) inhibitor treatment.

On October 11, 2021 Aura Biosciences, a clinical-stage oncology company developing a novel class of virus-like drug conjugate (VDC) therapies for multiple oncology indications, reported the presentation of interim Phase 2 data with 7 months average follow up evaluating the safety of suprachoroidal (SC) administration of AU-011, the Company’s lead product candidate for the first-line treatment of primary choroidal melanoma, as a part of the American Society of Retina Specialists (ASRS) 2021 Annual Meeting (Press release, Aura Biosciences, OCT 11, 2021, View Source [SID1234591082]).

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There have been no related serious adverse events, dose limiting toxicities, or grade 3 adverse events observed during the study. "These interim data presented today demonstrate that suprachoroidal administration may improve the therapeutic index and optimize treatment parameters," said Prithvi Mruthyunjaya, MD, MHS, Associate Professor of Ophthalmology and Director, Ocular Oncology Service, Byers Eye Institute at Stanford University, and presenter of the abstract. "I believe this approach may provide an opportunity for patients who need a new first line treatment for early-stage disease, where all current treatments are extremely invasive and unfortunately result in severe vision loss in many patients."

Phase 2 Trial Design and Timing

The Phase 2 trial is comprised of an open-label, dose escalation phase and a randomized, masked dose expansion phase that is assessing the safety and efficacy of ascending single- and repeat-doses of AU-011 via SC administration, followed by one or two laser applications per treatment. The randomized, dose expansion portion will be masked, sham-controlled and is designed to evaluate the safety and efficacy of the highest dose regimen of AU-011. Cohorts 1-5 have been fully enrolled (13 patients) and cohort 6 is currently enrolling in the Phase 2 study. The primary objective of the study is to assess safety and efficacy of AU-011 via SC administration for purposes of treating primary indeterminate lesions and choroidal melanoma.

The randomized phase of the trial is planned to begin in the second half of 2022 in patients with documented growth to establish the safety and efficacy of AU-011 and serve as the first pivotal trial for the treatment of indeterminate lesions and choroidal melanoma. The maximum treatment regimen anticipated for the randomized phase is three cycles of three weekly treatments of AU-011 at a dose of 80µg with 2 laser administrations.

Details from the ASRS 2021 Presentation:

Title: A Phase 2 Safety and Efficacy Trial of AU-011, a Virus-Like Drug Conjugate (VDC), with a Dose Escalation and a Randomized, Masked Expansion Phase
Presenter: Prithvi Mruthyunjaya, Stanford University
Session: Ocular Oncology Symposium
Date and Time: Monday, October 11, 2021 at 4:35pm ET

The presentation can be accessed by visiting the "Presentations" section of "News and Publications" page of the Aura Biosciences website.

About Choroidal Melanoma

Choroidal melanoma is a rare and aggressive type of eye cancer. Choroidal melanoma is the most common primary intraocular tumor in adults and develops in the uveal tract of the eye. No targeted therapies are available at present, and current radiotherapy treatments can be associated with severe visual loss and other long-term sequelae such as dry eye, glaucoma, cataracts, and radiation retinopathy. The most common current treatment is plaque radiotherapy, which involves surgical placement of a radiation device on the exterior of the eye over the tumor. The alternative is enucleation, or total surgical removal of the eye. Choroidal melanoma metastasizes in approximately 50 percent of cases with liver involvement in 80-90% of cases and, unfortunately, metastatic disease is universally fatal (source: OMF). There is a very high unmet need for a new vision sparing targeted therapy that could enable early treatment intervention for this life-threatening rare disease given the mortality rate in metastatic disease, lack of approved therapies, and the comorbidities of radioactive treatment options.

About AU-011

AU-011 is a first-in-class virus-like drug conjugate (VDC) therapy in clinical development for the first line treatment of choroidal melanoma. The virus-like component of the VDC selectively binds unique heparin sulphate proteoglycans (HSPGs), which are modified and overexpressed on the tumor cell surface of malignant cells in the choroid and AU-011 delivers a potent cytotoxic drug that is activated with infrared light. Upon activation with an ophthalmic laser, the cytotoxic drug rapidly and specifically disrupts the cell membrane of malignant cells with a pro-immunogenic cell death that can activate the immune system generating long term anti-tumor immunity. The unique specificity of tumor binding by the VDC enables the preservation of key eye structures, which may allow for the potential of preserving patients’ vision and reducing other long-term complications of radiation treatment. AU-011 can be delivered using equipment commonly found in an ophthalmologist’s office and does not require a surgical procedure, pointing to a potentially less invasive, more convenient therapy for patients and physicians. AU-011 for the treatment of choroidal melanoma is currently in Phase 2 clinical development and the company plans to expand the clinical program into choroidal metastasis.

About Suprachoroidal Administration

The suprachoroidal space (SCS) injection treatment approach offers unprecedented access to the back of the eye where sight-threatening disease often occurs. Aura believes that delivering AU-011 into SCS within the eye, has the potential to offer certain advantages, including higher bioavailability at the tumor site and reduced exposure of non-targeted tissues, which may lead to an improved therapeutic index for AU-011. Collectively, these features could allow for the treatment of a wider range of tumor sizes, and, therefore, a larger number of patients. The Company is partnered with Clearside Biomedical for use of Clearside’s SCS Microinjector for administration of AU-011 into the SCS. In preclinical research presented as part of the ARVO 2020 virtual program, AU-011 showed excellent distribution in the SCS, complete necrosis of tumors following laser activation in an animal model of choroidal melanoma and no clinical signs of anterior segment or posterior segment inflammation.

On October 11, 2021 PHYNOVA Group Ltd ("Phynova") and Membrahealth Marketing (M) Sdn Bhd ("Membra") reported a partnership on Reducose, Phynova’s patented and clinically researched White Mulberry Leaf extract that supports significant lowering of post-meal blood sugar and insulin response (Press release, Phynova, OCT 11, 2021, View Source [SID1234591066]).

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The partnership will encompass both distribution to Malaysian customers as well as joint promotion of the health benefits of Reducose. Membra will serve customers with Reducose as a stand-alone ingredient or as a hero-ingredient in turn-key solutions.

Stephane Ducroux, CEO at Phynova, said: "We are excited to embark on our go-to-market partnership with Membra in the Malaysian market. Phynova’s strategy is to partner with market focused experts such as Membra, who have a proven track record of building deep customer relationships, fast prototyping and turn-key solutions using ingredients with a strong science pedigree like Reducose.

Phynova produces Reducose 5%, a patented premium white mulberry leaf extract that can naturally reduce the blood sugar and insulin response after a meal by up to 40%. Reducose is vegetarian, plant based, allergen free and is backed by 6 human clinical studies. Most recently Phynova published its latest positive clinical trial results on Reducose in the peer-reviewed journal ‘Nutrition & Metabolism’. The full paper can be accessed here: View Source

Reducose has also won the 2020 Nutraingredients Asia ‘Ingredient of the year’ award in the healthy ageing category.

"We are proud to be associated with Phynova on Reducose, a product that we strongly believe can satisfy the demand of carbo- and sugar-loving as well as sugar-intolerant consumers in Malaysia" said Managing Director, Kenzi Loke of Membra Group.

On October 11, 2021 Immunis.AI, Inc., an immunogenomics platform company developing noninvasive blood-based tests to optimize patient care, reported the publication of pivotal results from its clinical trial, Evaluation of an RNAseq-based Immunogenomic Liquid Biopsy Approach in Early-Stage Prostate Cancer, in the journal Cells (Press release, ImmunisAI, OCT 11, 2021, View Source [SID1234591083]).

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Study findings validate the potential of the company’s proprietary Intelligentia platform to detect early-stage cancer and to stratify risk in men considering active surveillance of prostate cancer. The results also illustrate the potential of the company’s proprietary immunogenomic platform to address screening, treatment decision making, and minimal residual disease detection.

This is the first of three large, prospective studies completed and designed to demonstrate the power of the company’s proprietary Intelligentia platform for early-stage cancer detection and the assessment of disease aggressiveness.

Key Findings:

In this prospective study, the primary objective was to develop and validate a model for the identification of clinically significant prostate cancer. Peripheral blood samples were collected from 1,018 previously undiagnosed men undergoing prostate biopsy and split chronologically into independent training (n=713) and validation (n=305) sets. Whole transcriptome RNA sequencing was performed on isolated phagocytic CD14+ monocytes and non-phagocytic CD2+ lymphocytes and their gene expression levels were used to develop a predictive model that correlates to adverse pathologic features in early stage, clinically localized prostate cancer.

The immunotranscriptomic model, emphasizing both the tumor phagocytosis mechanism and the anti-tumor immune response, combined with clinical risk parameters, yielded an AUC (area under curve) of 0.83 on the independent validation set (n=305).
Notably, considering the average age at diagnosis of prostate cancer is 66, the model was the strongest predictor for adverse pathology in men 60-66 years of age with an AUC of 0.91 in the independent validation set.
Several cancer-related pathways appear to be significantly represented in the model gene set, including hedgehog signaling, epithelial mesenchymal transition, PDL1 and PD1 checkpoint, and transcriptional misregulation in cancer.
"The strong AUC generated in the study demonstrate high sensitivity and negative predictive value," said Dr. Kirk Wojno, Chief Medical Officer of Immunis.AI, "which together support the ability of our Intelligentia platform to deliver actionable information that can help urologists distinguish prostate cancer patients who may safely choose active surveillance from those who are harboring occult aggressive disease requiring immediate intervention."

"Immunis.AI is developing models incorporating both novel disease related biomarkers as well as the body’s immune response to that disease, so that a single blood sample can be bioinformatically assessed for the presence of multiple diseases simultaneously," said Dr. Leander Van Neste, Chief Scientific Officer of Immunis.AI.

"The data provide strong evidence that the Intelligentia platform delivers a combination of sensitivity and specificity for early-stage disease with the flexibility to interrogate multiple cancer types," Van Neste added. "We are encouraged by these results and excited about the potential of our platform for multi-cancer screening."

On October 11, 2021 Supernus Pharmaceuticals, Inc. (Nasdaq: SUPN) and Adamas Pharmaceuticals, Inc. (Nasdaq: ADMS), reported a definitive agreement for Supernus to acquire Adamas through a tender offer for $8.10 per share in cash (or an aggregate of approximately $400 million), payable at closing plus two non-tradable contingent value rights (CVR) collectively worth up to $1.00 per share in cash (or an aggregate of approximately $50 million), for a total consideration of $9.10 per share in cash (or an aggregate of approximately $450 million) (Press release, Supernus, OCT 11, 2021, View Source [SID1234591067]). The first CVR, worth $0.50 per share, is payable upon achieving net sales of GOCOVRI of $150 million in any four consecutive quarters between closing and the end of 2024. The second CVR, worth $0.50 per share, is payable upon achieving net sales of GOCOVRI of $225 million in any four consecutive quarters between closing and the end of 2025. The transaction is expected to close in late fourth quarter 2021 or in early first quarter 2022.

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The transaction will provide Supernus with two marketed products: GOCOVRI (amantadine) extended release capsules, the first and only U.S. Food and Drug Administration (FDA)-approved medicine indicated for the treatment of both OFF and dyskinesia in patients with Parkinson’s disease receiving levodopa-based therapy; and Osmolex ER (amantadine) extended release tablets, approved for the treatment of Parkinson’s disease and drug-induced extrapyramidal reactions in adult patients.

"This acquisition represents a significant step to further build a strong and diverse Parkinson’s disease portfolio, and aligns with our focus of acquiring value-enhancing, clinically-differentiated medicines to treat CNS diseases," said Jack Khattar, President and CEO of Supernus Pharmaceuticals. "We have a proven track record of strong commercial execution, and look forward to building on GOCOVRI’s growth momentum so that more patients can benefit from access to Adamas’ innovative neurological therapies."

Strategic and Financial Benefits

Strengthens Parkinson’s disease portfolio with GOCOVRI (amantadine) extended release capsules, the first and only FDA-approved medicine indicated for the treatment of both OFF and dyskinesia in patients with Parkinson’s disease receiving levodopa-based therapy.
Diversifies and increases revenue base and cash flow
Net sales of GOCOVRI were $71.2 million and $37.7 million in 2020 and for the first six months of 2021, respectively.
Combined with the acquisition of US WorldMeds CNS products in 2020, this transaction significantly reduces the reliance on net sales of Trokendi XR. In the first half of 2021 and on a combined proforma basis (including revenue from US WorldMeds and Adamas transactions), net sales of Trokendi XR represent 48% of Supernus revenues down from 72% (excluding revenue from these transactions).
Potential synergies of $60 million to $80 million in year one due to strong overlap with existing infrastructure.
The acquisition is expected to be significantly accretive in 2022.
"We are pleased that Supernus recognized the value created at Adamas and firmly believe this path forward is an excellent outcome for not only our shareholders, but all our stakeholders," said Neil F. McFarlane, Chief Executive Officer of Adamas Pharmaceuticals, Inc. "With their shared commitment to helping patients affected by neurological diseases and their extensive resources, Supernus can continue to advance our mission and reach. I am extremely proud of Team Adamas for their hard work and dedication to get us to this point and am confident that partnering with Supernus will maximize the potential of our innovative therapies."

Terms and Financing
Under the terms of the agreement, Supernus will commence a tender offer to acquire all outstanding shares of Adamas Pharmaceuticals, Inc. for a purchase price of $8.10 per share in cash (or an aggregate of approximately $400 million) payable at closing plus two non-tradable CVRs. All cash consideration will be funded through existing balance sheet cash.

The CVR entitles Adamas stockholders to receive up to an additional $1.00 per share in cash (or an aggregate of approximately $50 million) payable upon GOCOVRI achieving certain net sales milestones within specified periods (subject to the terms and conditions contained in a Contingent Value Rights Agreement detailing the terms of the CVRs). These milestones include (i) $0.50 per share payable if in any four consecutive quarters between closing and the end of 2024, net sales of GOCOVRI achieving $150 million, and (ii) another $0.50 per share payable if in any four consecutive quarters between closing and the end of 2025, net sales of GOCOVRI achieving $225 million. There can be no assurance any payments will be made with respect to the CVR.

Approvals and Timing of Close
The transaction, which has been approved by the boards of directors of both companies, is expected to close in late fourth quarter 2021 or in early first quarter 2022, subject to customary closing conditions, including receipt of required regulatory approvals and the tender of a majority of the outstanding shares of Adamas’ common stock. Following the successful closing of the tender offer, Supernus will acquire any shares of Adamas that are not tendered in the tender offer through a second-step merger at the same consideration as paid in the tender offer.

Full Year Financial Guidance
Supernus will provide full year 2022 financial guidance during the Company’s fourth quarter 2021 financial results conference call in February 2022.

Advisors
Jefferies LLC is acting as the exclusive financial advisor to Supernus. Lazard is acting as the exclusive financial advisor to Adamas. Saul Ewing Arnstein & Lehr LLP is serving as legal counsel and Grant Thornton is providing due diligence services to Supernus, and Cooley LLP is serving as legal counsel to Adamas.

Conference Call and Webcast today, October 11 at 8:30 a.m. ET
A conference call and a live webcast will be hosted today, October 11, at 8:30 a.m. ET, to discuss this transaction. Presentation slides will be available via this webcast link. A question and answer session with the Supernus management team will follow the company’s remarks.

Please refer to the information below for conference call dial-in information and webcast registration. Callers should dial in approximately 10 minutes prior to the start of the call.

Conference dial-in: (877) 288-1043
International dial-in: (970) 315-0267
Conference ID: 6685281
Conference Call Name: Supernus Pharmaceuticals Business Update Call
Following the live call, a replay will be available on the Company’s website, www.supernus.com, under "Investor Relations".