On January 8, 2019 SELLAS Life Sciences Group, Inc. (Nasdaq: SLS) ("SELLAS" or the "Company"), a clinical-stage biopharmaceutical company focused on the development of novel cancer immunotherapies for a broad range of cancer indications, reported a corporate update on the Company’s clinical development of galinpepimut-S (GPS) and nelipepimut-S (NPS), which are both in late-stage development (Press release, Sellas Life Sciences, JAN 8, 2019, View Source [SID1234532580]).

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"In 2018, SELLAS achieved significant progress towards our corporate and clinical goals, as we advanced our immunotherapy pipeline and completed our first year as a public company," said Dr. Angelos M. Stergiou, MD, ScD h.c., President and Chief Executive Officer of SELLAS. "As we look to 2019, we are excited to initiate our pivotal Phase 3 program for GPS in acute myeloid leukemia (AML), and are in active discussions with the U.S. Food and Drug Administration (FDA) regarding the registration-enabling Phase 3 trial and potential consideration for accelerated approval and breakthrough designation for NPS to treat triple negative breast cancer. We also are exploring the potential of GPS in combination with pembrolizumab in additional tumor types in the context of a Phase 1/2 basket clinical study and look forward to continued progress across our broad pipeline in the year ahead."

Galinpepimut-S (GPS)

In November 2018, SELLAS aligned with the FDA on the clinical trial design and biostatistical plan for a Phase 3 registrational study for GPS in acute myeloid leukemia (AML). The planned Phase 3 registrational study will be a 1:1 randomized, open-label study comparing GPS in the maintenance setting to investigators’ choice of best available treatment (BAT) in adult AML patients who have achieved hematologic complete remission, with or without thrombocytopenia (CR2/CR2p), after second-line antileukemic therapy and who are deemed ineligible for or unable to undergo allogeneic stem-cell transplantation. This study will serve as the basis for a Biologics License Application (BLA) submission, subject to positive results, and SELLAS expects to start the Phase 3 trial in the second quarter of 2019.

The Phase 3 study is expected to enroll approximately 116 patients at approximately 50 clinical sites in the United States and Europe. The primary endpoint is overall survival (OS) and secondary endpoints include leukemia-free survival, antigen-specific T-cell immune response dynamics over time and rates of achievement of measurable residual disease (MRD) negativity. The study will have a planned interim safety and futility analysis after 80 events, expected to occur in the third quarter of 2020. GPS was previously granted Fast Track and Orphan Drug designations by the FDA for the treatment of AML.

In December 2018, SELLAS initiated enrollment of the Phase 1/2 open-label, non-comparative, multicenter, multi-arm study of GPS in combination with Merck’s anti-PD-1 therapy KEYTRUDA (pembrolizumab) in patients with selected WT1-positive advanced cancers, including both hematologic malignancies and solid tumors. This study, which is being conducted under a Clinical Trial Collaboration and Supply Agreement (CTSA) with Merck (known as MSD outside the United States and Canada), will assess the efficacy and safety of the combination, with exploratory long-term follow-up for overall survival and safety. The study will enroll approximately 90 patients at up to 20 centers in the United States. The initial tumor types to be treated will be acute myelogenous leukemia (AML) (patients unable to attain deeper morphological response than partial on hypomethylating agents and who are not eligible for allogeneic hematopoietic stem cell transplant) and ovarian cancer (second or third line), to be followed by triple negative breast cancer (second line), small cell lung cancer (second line), and colorectal cancer (third or fourth line).

Nelipepimut-S (NPS)

Based on promising Phase 2b data presented in 2018, SELLAS is currently in continuing active discussions with the FDA regarding the optimal development path for NPS in triple negative breast cancer (TNBC).

In the Phase 2b study of trastuzumab (Herceptin) +/- nelipepimut-S (NPS) in HER2 low-expressing breast cancer patient cohorts, trastuzumab + NPS demonstrated clinically and statistically significant efficacy in the TNBC cohort, with a p-value of 0.013 and a 75.2% reduction in risk of relapse or death. In October 2018, the Data Safety Monitoring Board (DSMB) unanimously concluded that the final analysis of the Phase 2b study data with a median follow-up of 26 months confirmed that TNBC patients should be the key target population for the development of trastuzumab + NPS in the adjuvant setting in early-stage HER2 1+/2+ breast cancer patients.

A preplanned secondary efficacy analysis across human leukocyte antigen (HLA) allele subgroups from the Phase 2b study confirmed the therapeutic potential of NPS in patients with early-stage TNBC in the adjuvant setting across HLA types A-02, -03, -24 and -26, which cover approximately 80-85% of the North American/European populations and 86-90% of Asian/Pacific basin populations.

Additional positive data from the Phase 2b study showed a clinically meaningful and statistically significant decrease in the number of clinically detectable relapses in the TNBC cohort with the combination of trastuzumab + NPS (7.5%) vs. trastuzumab alone (27.3%) (p=0.004). In addition, four pre-defined subgroups of TNBC patients in the trastuzumab + NPS arm demonstrated an average decrease of 84.2% in relative risk of relapse or death at 24 months (p=0.004-0.014).

In a Type C meeting with the FDA, SELLAS discussed several key points of the clinical and regulatory strategy for NPS in combination with trastuzumab for TNBC, including potential for accelerated approval; a registration-enabling Phase 3 trial design and biostatistical plan; and the potential for breakthrough designation. SELLAS expects a further meeting with the FDA in early 2019 regarding the potential for breakthrough designation as well as an additional meeting in the first quarter of 2019 to reach agreement for a final development program for NPS in TNBC.

An abstract summarizing the comprehensive set of results from the final analysis of the NPS + trastuzumab Phase 2b clinical study has been accepted for an oral presentation at the ASCO (Free ASCO Whitepaper)-SITC Clinical Immuno-Oncology Symposium in San Francisco, CA, on March 2, 2019 at 10:15 AM.

NPS was previously granted Fast Track designation by the FDA for the adjuvant treatment of patients with early stage breast cancer with low to intermediate HER2 expression following standard of care upfront therapy (surgery plus chemotherapy +/- radiotherapy).

Expected 2019 Clinical Milestones

Regulatory and development program with FDA for NPS in TNBC patients finalized in Q1 2019.
Phase 3 registration-enabling study of GPS in AML patients initiated in Q2 2019, with a planned interim analysis expected in Q3 2020.
Interim analysis of Phase 1/2 basket study of GPS with pembrolizumab in multiple tumor types in Q4 2019.
Herceptin and Keytruda are registered trademarks of Genentech, Inc. and Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, N.J., USA., respectively, and are not trademarks of SELLAS. The manufacturers of these brands are not affiliated with and do not endorse SELLAS or its products.

On January 8, 2019 ImmunoGen, Inc. (Nasdaq: IMGN), a leader in the expanding field of antibody-drug conjugates (ADCs) for the treatment of cancer, reported the sale of its residual rights to receive royalty payments on commercial sales of Kadcyla (ado-trastuzumab emtansine) to OMERS, the defined benefit pension plan for municipal employees in the Province of Ontario, Canada, for $65 million (Press release, ImmunoGen, JAN 8, 2019, View Source [SID1234553884]).

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"ImmunoGen played a key role in the generation and early development of Kadcyla, the first ADC approved for the treatment of HER2-positive breast cancer, and we are pleased to see the continued progress of this important therapy in the market," said Mark Enyedy, President and Chief Executive Officer. "As ImmunoGen evolves into a fully-integrated company with our proprietary portfolio, this transaction further strengthens our balance sheet as we execute on our strategic priorities and work to deliver more good days to people living with cancer."

This transaction entails the sale of the residual interest held by ImmunoGen from a prior transaction with Immunity Royalty Holdings, L.P. (IRH). In 2015, ImmunoGen announced a $200 million non-dilutive royalty transaction through which ImmunoGen sold the right to receive 100% of the royalty revenue on Kadcyla commercial sales to an undisclosed threshold amount, subject to certain conditions. Once the applicable threshold was met, ImmunoGen would receive 85% of the Kadcyla royalty revenue and the original purchaser would receive 15% for the remaining term of the royalty. With this transaction, OMERS now owns 100% of ImmunoGen’s rights to receive Kadcyla royalties.

MTS Health Partners, L.P. acted as exclusive financial advisor to ImmunoGen and Mintz, Levin, Cohn, Ferris, Glovsky and Popeo, P.C. acted as special transactional counsel to ImmunoGen.

ABOUT KADCYLA ROYALTIES

Genentech, a member of the Roche Group, developed Kadcyla (ado-trastuzumab emtansine) using ADC technology licensed from ImmunoGen under a 2000 agreement established between the companies. This agreement entitles ImmunoGen to receive royalties ranging from 3-5% on Kadcyla sales in countries where ImmunoGen holds valid patents covering Kadcyla, and 2% in countries without relevant ImmunoGen patents. ImmunoGen is entitled to receive royalties on commercial Kadcyla sales in each country for ten years after the launch of Kadcyla in that country. This period extends to twelve years for each country in which ImmunoGen has valid claims in relevant patents on the tenth anniversary of the commercial launch of Kadcyla in that country.

On January 8, 2019 Innovation Pharmaceuticals (OTCQB:IPIX) ("the Company"), a clinical stage pharmaceutical company, is pleased to inform shareholders of recent articles published in "The Lancet," a leading independent, international journal for medical professionals, detailing data from two, separate clinical studies1,2 of radiotherapy plus ERBITUX (cetuximab) or cisplatin in treating oropharyngeal cancer, a type of Head and Neck Cancer (HNC) (Press release, Innovation Pharmaceuticals, JAN 8, 2019, View Source [SID1234532565]).

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The findings from the large studies are particularly great news for the Company and relevant for development of Brilacidin oral rinse under a U.S. Food and Drug Administration (FDA) Fast Track designation as a new drug candidate for the prevention and treatment of severe Oral Mucositis (OM) in HNC patients receiving chemoradiation.

Cetuximab, an Epidermal Growth Factor Receptor inhibitor, has been hypothesized as a less toxic option to cisplatin, a drug commonly used today in combination with radiotherapy in HNC treatment regimens. While effective, cisplatin is known to have certain toxicities, including frequently causing severe OM, a debilitating and painful side effect characterized by lesions in the mouth’s mucosa that can force suspension of cancer therapy, render a patient unable to eat or drink and increase risk of sepsis, among other complications. There are currently no FDA-approved drugs for the prevention and treatment of OM for patients with solid tumors.

In each study, replacing cisplatin/radiotherapy with cetuximab/radiotherapy delivered inferior results when evaluated for overall survival, progression-free survival, or tumor control and no difference in overall severe toxicity. Although each study should be considered landmark on its own, the harmonized results are most notable in showing that the combination of cisplatin and radiotherapy will remain a standard of care in treating HNC.

"These data indicate that a cisplatin/radiotherapy regimen is likely to continue to be a mainstay in treating HNC, in spite of the drug commonly causing severe OM. A glaring critical void in patient care — and, thus, comprising a tremendous market opportunity for the Company — is in developing a safe and effective treatment that can become part of the standard regimen to prevent severe OM," commented Arthur P. Bertolino, MD, PhD, MBA, President and Chief Medical Officer at Innovation Pharmaceuticals. "We are highly confident that Brilacidin oral rinse could fill that large therapeutic gap in cancer care and give patients preventative relief from a frequently occurring and horrible consequence of chemoradiation."

In the Company’s successfully completed Phase 2 trial, Brilacidin oral rinse significantly reduced the incidence of severe OM (WHO Grade ≥ 3) in HNC patients receiving cisplatin administered 80-100 mg/m2 every 21 days in combination with radiotherapy. In this patient population, incidence of severe OM was reduced to 25.0 percent in the modified Intent-to-Treat population, versus 71.4 percent of placebo patients. In the Per Protocol patient group, incidence of severe OM dropped to 14.3 percent for patients receiving Brilacidin, compared to 72.7 percent among those receiving placebo.

The Company recently completed an End-of-Phase 2 meeting with the FDA, paving the way for pivotal trials of Brilacidin oral rinse for HNC patients receiving chemoradiation. In Phase 3 trials, Brilacidin will be evaluated in patients receiving aggressive chemotherapy (cisplatin administered 80-100 mg/m2 every 21 days) and in those receiving less aggressive chemotherapy (cisplatin administered 30-40 mg/m2 weekly) as part of the chemoradiation regimen.

In its goal to build a world-class clinical asset across the Brilacidin franchise, with the indication of severe OM a Company priority, Innovation Pharmaceuticals is preparing to seek scientific advice from the European Medicines Agency to round out European Union program requirements for Phase 3 clinical trials.

On January 8, 2019 Moderna, Inc. (Nasdaq: MRNA), a clinical stage biotechnology company pioneering messenger RNA (mRNA) therapeutics and vaccines to create a new generation of transformative medicines for patients, reported recent updates to several of its immuno-oncology and rare disease programs and outlined its 2019-2020 corporate objectives (Press release, Moderna Therapeutics, JAN 8, 2019, View Source [SID1234532581]). Moderna has 21 mRNA development candidates in its pipeline, with 11 programs now in clinical development.

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"This year we are focused on making significant advances to our pipeline as we work to bring multiple programs into Phase 2 clinical trials, move programs within our rare disease portfolio toward the clinic and leverage our mRNA platform to create both new development candidates and potential new modalities where we believe there is an opportunity to develop therapies for a broad range of diseases," said Stéphane Bancel, Moderna’s Chief Executive Officer. "I am pleased with the continued progress of our pipeline, our ability to now manufacture mRNA for clinical development at our new site in Norwood and the relentless work of our team. I believe we are better positioned than we have ever been to deliver on the promise of our science to bring forward mRNA medicines that have the potential to improve the lives of patients."

Mr. Bancel will present a company overview and strategy update today at 10:30am PST at the 37th Annual J.P. Morgan Healthcare Conference in San Francisco. A live webcast of today’s presentation can be found at investors.modernatx.com.

Detailed program updates:

Intratumoral Immuno-oncology: These programs aim to drive anti-cancer T cell responses by injecting mRNA therapies directly into tumors.

OX40L (mRNA-2416): Based on previously reported clinical observations in two patients with advanced ovarian carcinoma in its Phase 1 study, Moderna has submitted an Investigational New Drug (IND) amendment to the U.S. Food and Drug Administration (FDA) and to the study’s clinical research sites to commence a Phase 2 cohort of mRNA-2416 as a monotherapy in advanced ovarian carcinoma within its current Phase 1 study. Thus far, 28 patients have been dosed in the ongoing Phase 1 trial for mRNA-2416, an open-label, multicenter study of repeated intratumoral injections of mRNA-2416 in patients with advanced relapsed/refractory solid tumor malignancies and lymphomas. Initial data from the Phase 1 study were presented in a poster session at the Annual Meeting of the Society for Immunotherapyof Cancer in November 2018.
OX40L + IL23 + IL36γ (Triplet) (mRNA-2752):Moderna has dosed the first patient in the Phase 1 study of mRNA-2752, an intratumoral injection comprising three mRNAs encoding for OX40L + IL23 + IL36γ for the treatment of advanced or metastatic solid tumor malignancies or lymphoma. The open label, multi-center study is evaluating the safety and tolerability of mRNA-2752 as a single agent and in combination either with AstraZeneca’s durvalumab or tremelimumab, and will assess anti-tumor activity, protein expression in tumors and pharmacokinetics, and exploratory endpoints that include assessment of immunological response.
Cancer Vaccines: These programs focus on stimulating a patient’s immune system to tumor-related antigens to enable the immune system to elicit a more effective antitumor response.

Personalized Cancer Vaccine (PCV) (mRNA-4157): Moderna and Merck areplanning a randomized Phase 2 study comparing PCV and KEYTRUDA against KEYTRUDA alone. To date, interim Phase 1 PCV study data from 24 patients showed no dose limiting toxicities up to 0.39 mg (the third of four dose levels). Interim Phase 1 immunogenicity data have also been collected in certain patients dosed with mRNA-4157 as a monotherapy, and potential antigen-specific T cell responses have been detected. The Phase 1 study continues in the dose-escalation phase of the protocol.
KRAS vaccine (mRNA-5671): Merck will lead an open-label, multi-center, dose-escalation and dose-expansion Phase 1 study to evaluate the safety and tolerability of mRNA-5671 administered as an intramuscular injection both as a monotherapy and in combination with KEYTRUDA. KRAS is a frequently mutated oncogene in epithelial cancers, primarily in non-small cell lung, colorectal and pancreatic cancers. The IND for a KRAS vaccine was originally submitted by Moderna and included an mRNA for the membrane protein STimulator of INterferon Gene (STING) to help promote antitumor activity. That IND was transferred to Merck which now will move the program forward under the same IND with KRAS as the sole mRNA. Merck may choose to include STING mRNA in later clinical development of the KRAS vaccine.
Systemic Intracellular Therapeutics: These programs aim to deliver mRNA into cells within target organs as a therapeutic approach for diseases caused by a missing or defective protein.

Methylmalonic Acidemia (MMA) (mRNA-3704): An IND application has been submitted to the FDA for mRNA-3704, Moderna’s development candidate for MMA. If approved, this will be Moderna’s first rare disease program to advance into clinical trials. The Company plans to conduct an open-label, multi-center, dose escalation Phase 1/2 study of multiple ascending doses of mRNA-3704 in pediatric patients with isolated MMA due to MUT enzyme deficiency. The objectives of the study are to evaluate safety and tolerability. mRNA-3704 has received Rare Pediatric Disease Designation by the FDA and Orphan Drug Designation by both the FDA and the European Medicines Agency.
Propionic Acidemia (PA) (mRNA-3927): mRNA-3927 was granted Orphan Drug Designation by the FDA in December 2018 and Rare Pediatric Disease Designation by the FDA in January 2019. PA is a rare, life-threatening, inherited metabolic disorder due to a defect in the mitochondrial enzyme propionyl-CoA carboxylase, or PCC. It primarily affects the pediatric population and there is no approved therapy. Moderna is continuing to advance mRNA-3927 in pre-clinical studies. Moderna also continues to enroll patients in a global natural history study of MMA and PA (MaP Study) designed to identify and correlate clinical and biomarker endpoints for these disorders. This is a global, multi-center, non-interventional study for patients with confirmed diagnosis of MMA due to methylmalonyl-CoA mutase (MUT) deficiency or PA.
More than 760 subjects have been dosed with a therapeutic or vaccine candidate developed with Moderna’s mRNA technology.

Information about each program in Moderna’s pipeline, including those discussed in this press release, can be found on our investor relations page of our website www.modernatx.com.

Corporate Objectives:

Moderna shared its corporate objectives for 2019 – 2020, which include:

1. Generate human proof-of-concept data for multiple medicines
2. Execute on current development pipeline
3. Create new development candidates in existing modalities
4. Invent new modalities

Corporate Updates:

Continued growth across organization:Moderna ended 2018 with approximately 735 full time employees. The Company ended 2017 with 535 employees.

Continued strong cash position: We expect our cash, cash equivalents, and investments in marketable securities as of December 31, 2018 to be approximately $1.7 billion (unaudited), as compared to $902 million (audited) as of December 31, 2017. The year over year increase includes approximately $564 million (unaudited) in net proceeds from our initial public offering completed in December 2018, approximately $661 million in net proceeds from our preferred stock issuances in 2018, and a $13 million (unaudited) premium associated with the 2018 amended and restated personalized cancer vaccines agreement with Merck & Co.

On January 8, 2019 Astellas Pharma Inc. (TSE: 4503, President and CEO: Kenji Yasukawa, Ph.D., "Astellas") reported that gonadotrophin-releasing hormone (GnRH) receptor antagonist, Gonax received approval for partial changes for the additional dosage and administration of Gonax for the treatment of prostate cancer at 12-week intervals, and obtained manufacturing and marketing authorization for Gonax 240 mg in Japan (Press release, Astellas, JAN 8, 2019, View Source [SID1234534620]).

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Gonax is a GnRH receptor antagonist with a subcutaneously injectable formulation. Astellas acquired exclusive development and commercialization rights of Gonax for the use of prostate cancer treatment in Japan from Ferring Pharmaceuticals in January 2006, and launched Gonax for the indication of prostate cancer in Japan in October 2012.

GnRH is a hormone synthesized and released from the hypothalamus in the brain and is involved in the production of the male hormone testosterone thorough binding to the GnRH receptors in the pituitary gland. Although testosterone is an important hormone that plays a central role in the maintenance of male function, it also stimulates prostate cancer to grow and to spread out and in result, often aggravates symptoms in prostate cancer patients. Gonax competitively inhibits the binding of GnRH to the GnRH receptors and controls the growth of prostate cancer by suppressing the testosterone.

Astellas believes that adding the maintenance dose of Gonax 480 mg at 12-week intervals to the maintenance dose of Gonax 80 mg at 4-week intervals will improve convenience for patients and reduce the burden on patients and further contribute to the treatment of prostate cancer.

Astellas reflected the impact from this approval in its financial forecasts of the current fiscal year ending March 31, 2019.