Alnylam Pharmaceuticals, Inc. | October 07, 2022
Alnylam Pharmaceuticals, Inc. the leading RNAi therapeutics company, announced that the U.S. Food and Drug Administration approved a label expansion for OXLUMO® an RNAi therapeutic administered via subcutaneous injection, now indicated for the treatment of primary hyperoxaluria type 1 to lower urinary oxalate and plasma oxalate levels in pediatric and adult patients. The approval is based on positive efficacy and safety results of the ILLUMINATE-C Phase 3 study of OXLUMO in patients with severe renal impairment, including those on hemodialysis.
PH1 is an ultra-rare genetic disease characterized by oxalate overproduction in the liver. The excess production of oxalate results in the deposition of calcium oxalate crystals in the kidneys and urinary tract and can lead to the formation of painful and recurrent kidney stones and nephrocalcinosis, which can progress to kidney failure. PH1 can also lead to oxalate deposition in multiple organs beyond the kidney, a condition known as systemic oxalosis.
The label expansion for OXLUMO is based on positive six-month results from ILLUMINATE-C, where treatment with lumasiran resulted in a substantial reduction in POx from baseline to Month Six in both dialysis-independent and -dependent patients. Patients in both cohorts had a reduction in POx as early as Month One. In Cohort A treatment with OXLUMO led to a 33% least squares (LS) mean reduction in POx from baseline to Month Sixand in Cohort B, treatment with OXLUMO led to a 42% LS mean reduction in POx from baseline to Month Six. OXLUMO demonstrated an encouraging safety and tolerability profile with no deaths or drug-related serious adverse events among enrolled patients. There were two treatment discontinuations due to adverse events in the extension period of the study, neither of which was drug related. The most common AE related to lumasiran was injection-site reaction reported in five of 21 patients which were all mild and transient.
“The significance of the label expansion of OXLUMO cannot be overstated, as this milestone provides crucial reassurance among a patient population with the highest unmet need, as well as their caregivers and loved ones, that OXLUMO is available in the US for patients living with PH1, including those with advanced disease. We are grateful to Alnylam for their continued commitment to the PH1 community and for ensuring that all patients — no matter how severe their disease — have the same opportunity to potentially benefit from OXLUMO treatment.”
Kim Hollander, Executive Director of the Oxalosis and Hyperoxaluria Foundation
In November of 2020, OXLUMO was approved by the FDA for the treatment of PH1 to lower UOx levels in pediatric and adult patients. It was also approved by the European Medicines Agency (EMA) for the treatment of PH1 in all age groups. The Committee for Medicinal Products for Human Use (CHMP) of the EMA delivered a positive opinion recommending variation to the marketing authorization of OXLUMO based on ILLUMINATE-C data from patients with advanced PH1 in September 2022. Lumasiran is also being evaluated in a global Phase 2 study as an investigational treatment in patients with recurrent kidney stone disease and elevated UOx levels.
OXLUMO® is an RNAi therapeutic targeting hydroxyacid oxidase 1. HAO1 encodes glycolate oxidase. Thus, by silencing HAO1 and depleting the GO enzyme, OXLUMO inhibits production of oxalate – the metabolite that directly contributes to the pathophysiology of PH1. OXLUMO utilizes Alnylam’s Enhanced Stabilization Chemistry GalNAc-conjugate technology, which enables subcutaneous dosing with increased potency and durability and a wide therapeutic index. OXLUMO has received regulatory approvals from the U.S. Food and Drug Administration for the treatment of primary hyperoxaluria type 1 to lower urinary and plasma oxalate levels in pediatric and adult patients and from the European Medicines Agency for the treatment of PH1 in all age groups.
In the pivotal ILLUMINATE-A study, OXLUMO was shown to significantly reduce levels of urinary oxalate relative to placebo, with the majority of patients reaching normal or near-normal levels. In the ILLUMINATE-B pediatric Phase 3 study, OXLUMO demonstrated an efficacy and safety profile consistent to that observed in ILLUMINATE-A. In the ILLUMINATE-C study, OXLUMO resulted in substantial reductions in plasma oxalate in patients with advanced PH1. Across all three studies, injection site reactions were the most common drug-related adverse reaction.
OXLUMO is administered via subcutaneous injection once monthly for three months, then once quarterly beginning one month after the last loading dose at a dose based on actual body weight. For patients who weigh less than 10 kg, ongoing dosing remains monthly.
About Alnylam Pharmaceuticals
Alnylam has led the translation of RNA interference into a whole new class of innovative medicines with the potential to transform the lives of people afflicted with rare and prevalent diseases with unmet need. Based on Nobel Prize-winning science, RNAi therapeutics represent a powerful, clinically validated approach yielding transformative medicines. Since its founding 20 years ago, Alnylam has led the RNAi Revolution and continues to deliver on a bold vision to turn scientific possibility into reality. Alnylam’s commercial RNAi therapeutic products are ONPATTRO® GIVLAARI® OXLUMO® AMVUTTRA® and Leqvio® being developed and commercialized by Alnylam’s partner, Novartis. Alnylam has a deep pipeline of investigational medicines, including six product candidates that are in late-stage development. Alnylam is executing on its “Alnylam P5x25” strategy to deliver transformative medicines in both rare and common diseases benefiting patients around the world through sustainable innovation and exceptional financial performance, resulting in a leading biotech profile. Alnylam is headquartered in Cambridge, MA.
Eyenovia, Inc. | November 30, 2022
Eyenovia, Inc. a pre-commercial ophthalmic technology company developing the Optejet® delivery system for use both in combination with its own drug-device therapeutic programs for mydriasis, presbyopia and pediatric progressive myopia as well as out-licensing for additional indications, announced that the company has entered into a $15 million credit facility with the Avenue Venture Opportunities Fund, L.P. The financing is intended to support manufacturing in anticipation of a MydCombi launch and clinical supply for ongoing programs.
Per the terms of the agreement, Eyenovia received $10 million of gross proceeds at closing. The additional $5 million will be available, at the company’s option, should MydCombi™ be approved for marketing in the U.S. by the Food and Drug Administration by August 2023. The Avenue facility replaces the company’s Silicon Valley Bank facility, which was recently paid off.
“We are pleased to have the support of Avenue through this credit facility at terms which create minimal dilution as compared to a traditional equity capital raise. Together with our existing cash on-hand, we expect the additional capital provided by this facility to fund our operations through at least late 2023 or early 2024, or through value creating milestones, including the potential approval of MydCombi™ and preparations for the possible submission of a New Drug Application for our novel presbyopia treatment, MicroLine™.”
Michael Rowe, chief executive officer of Eyenovia
“We are pleased to provide this financing to Eyenovia as we believe its Optejet dispensing technology truly differentiates the company from its peers and offers great potential across a broad range of high value ophthalmic indications,” stated Chad Norman, Senior Portfolio Manager of the Avenue Venture Debt Fund.
Eyenovia’s current pro-forma unrestricted cash balance, including approximately $9.5 million of net proceeds from this facility, is approximately $25.5 million.
About Eyenovia, Inc.
Eyenovia, Inc. is an ophthalmic pharmaceutical technology company developing a pipeline of microdose array print therapeutics. Eyenovia is currently focused on the late-stage development of microdosed medications for mydriasis, presbyopia and myopia progression.
About Avenue Venture Opportunities
The Avenue Venture Debt Fund seeks to provide creative financing solutions to high-growth, venture capital-backed technology and life science companies. The Avenue Venture Debt Opportunities Fund focuses generally on companies within the underserved segment of the market created by the widening financing gap between commercial banks and larger debt funds. The Avenue Venture Debt fund is part of the larger group of funds of Avenue Capital Group. For additional information on Avenue Capital Group, which is a global investment firm with assets estimated to be approximately $12.3 billion as of October 31, 2022.
Advaxis and Ayala Pharmaceuticals | October 20, 2022
Ayala Pharmaceuticals, Inc. a clinical-stage oncology company focused on developing and commercializing small molecule therapeutics for patients suffering from rare tumors and aggressive cancers and Advaxis, Inc. a biotechnology company devoted to the discovery, development and commercialization of immunotherapies based on a technology which uses engineered Listeria monocytogenes, today announced that they have entered into a definitive merger agreement. The merger would result in a combined company that will focus predominantly on the development and commercialization of Ayala’s lead program AL102 for the treatment of desmoid tumors and Advaxis’s candidate ADXS-504 in development for prostate cancer.
Kenneth A. Berlin, President and Chief Executive Officer of Advaxis, said, “Advaxis took a thorough approach in our quest to find the right partner with the right products. This merger is expected to enhance Advaxis’s portfolio of clinical assets, with Ayala’s proprietary gamma secretase inhibitors that are being developed as targeted therapies for rare and aggressive tumors. Ayala’s lead candidate, AL102, is currently being investigated in the Phase 2/3 RINGSIDE study in desmoid tumors, which we believe will accelerate the stage of product development for the combined company dramatically. We are particularly excited about very promising interim data from RINGSIDE, which showed that AL102 monotherapy had meaningful anti-tumor activity with tumor shrinkage in the majority of patients that appeared to be deepening over time. The combined management team has extensive commercial and R&D experience, and we believe we have the cash to advance the combined portfolio through key milestones in 2023, including longerterm data from Part A of RINGSIDE, clarity on the registration path for AL101 in recurrent/metastatic adenoid cystic carcinoma (ACC) and initial clinical and PSA data from the Phase 1 trial of ADXS-504 in prostate cancer. We believe that this transaction will also help drive our efforts to return to a Nasdaq listing and enhance our ability to access capital.”
“We are pleased to announce the proposed merger with Advaxis, which is expected to provide our pipeline and AL102 with additional financial resources as well as additional infrastructure in the U.S. The two companies have a shared mission to develop innovative therapies to improve the lives of patients with cancer and I believe we have found a good partner to advance our pipeline and create value for our stakeholders.”
Roni Mamluk, Ph.D., President and Chief Executive Officer of Ayala
Consummation of the merger is subject to certain closing conditions, including, among other things, approval by the stockholders of Ayala. At the closing of the merger, Ayala will be delisted from The Nasdaq Global Market. The combined company’s common stock is expected to begin trading on the OTCQX at the effective time of the merger, subject to Advaxis’ planned efforts to have the stock of the combined company listed on Nasdaq, as to which no assurances can be made.
About Ayala Pharmaceuticals, Inc.
Ayala Pharmaceuticals, Inc. is a clinical-stage oncology company focused on developing and commercializing small molecule therapeutics for patients suffering from rare tumors and aggressive cancers. Ayala’s approach is focused on predicting, identifying and addressing tumorigenic drivers of cancer through a combination of its bioinformatics platform and next-generation sequencing to deliver targeted therapies to underserved patient populations. The company has two product candidates under development, AL101 and AL102, targeting the aberrant activation of the Notch pathway with gamma secretase inhibitors to treat a variety of tumors, including adenoid cystic carcinoma and desmoid tumors. AL102 has received Fast Track Designation from the U.S. FDA and is currently in the Phase 3 portion of a pivotal study for patients with desmoid tumors. AL101 has received Fast Track Designation and Orphan Drug Designation from the U.S. FDA and is currently in a Phase 2 clinical trial for patients with ACC bearing Notch activating mutations.
About Advaxis, Inc.
Advaxis, Inc. is a clinical-stage biotechnology company focused on the development and commercialization of proprietary Lm-based antigen delivery products. These off-the-shelf immunotherapies are a significant advancement in immunotherapy as they integrate multiple functions into a single therapy by directing antigen presenting cells to stimulate T-cells and other components of the immune system, while reducing tumor protection in the tumor microenvironment, facilitating the elimination of tumors. The company has two programs in the clinic: ADXS-503 for late-stage lung cancer and ADXS-504 for early-stage prostate cancer.