On January 10, 2021 Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY), the leading RNAi therapeutics company, reported its new 5-year strategy "Alnylam P5x25" focused on the Company’s planned transition to a top-5 biotech (measured by market capitalization) in the next 5 years through: sustainable innovation yielding transformative medicines for rare and common diseases for patients around the world and delivery of exceptional financial performance (Press release, Alnylam, JAN 10, 2021, View Source [SID1234573944]). Alnylam P5x25 extends the Company’s decade-long heritage of providing longer term, 5-year business strategy guidance, the most recent of which was known as Alnylam 2020. In addition, Alnylam today reported preliminary fourth quarter and full year 2020 global net product revenues for ONPATTRO and GIVLAARI and provided additional updates on the Company’s commercial launches, including initial OXLUMO demand.

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New 5-Year Strategy: P5x25
Alnylam ended last year exceeding all metrics for its Alnylam 2020 strategy, with 4 marketed products (versus 3), 12 clinical programs (versus 10), 6 of which are in late-stage development (versus 4), across 4 strategic therapeutic areas (versus 3).

The Company’s Alnylam P5x25 strategy is aimed at Alnylam’s transition to a top 5 biotech company, as measured by market capitalization, over the next 5 years.

Specifically, the Company intends to end 2025 with the following profile**:

Patients: Over 0.5 million on Alnylam RNAi therapeutics globally
Products: 6 or more marketed products in rare and prevalent diseases
Pipeline: Over 20 clinical programs, with 10 or more in late stages and 4 or more INDs per year
Performance: ≥40% revenue CAGR through YE 2025
Profitability: Achieve sustainable non-GAAP profitability within the period
"We executed well on our Alnylam 2020 strategy, exceeding all pre-set metrics and transitioning into a global, multi-product commercial company with a robust clinical pipeline and an organic product engine delivering sustainable innovation, a profile that has rarely been achieved in biotech history. It was especially gratifying to cap 2020 with positive Phase 3 HELIOS-A results for vutrisiran, which is set to become our 5th RNAi therapeutic to reach the market, if approved," said John Maraganore, Ph.D., CEO of Alnylam Pharmaceuticals. "We are now thrilled to launch our new chapter with Alnylam P5x25, which is aimed at Alnylam’s planned transition to a top 5 biotech in market capitalization based on a proven and high-yielding technology for disruptive medical innovation and a foundational track record of commercial execution. Indeed, with Alnylam P5x25, we expect to sustainably and organically create and commercialize transformative rare and common disease medicines benefiting hundreds of thousands of patients around the world while delivering strong financial performance and profitability, resulting in a leading biotech profile."

2020 Preliminary Commercial and Financial Performance*
ONPATTRO (patisiran), a commercial-stage RNAi therapeutic targeting transthyretin (TTR) for the treatment of polyneuropathy in adult patients with hATTR amyloidosis.

Preliminary global net product revenues for the fourth quarter and full year 2020 were approximately $90 million and $306 million, respectively.
Q4 results represent approximately 10 percent growth compared to Q3 and include 10 percent growth in the U.S. market segment driven by new patient demand.
Further, the full year ONPATTRO revenues reached the high end of the previously shared guidance range of $295 million – $310 million and represent over 80 percent growth from full year 2019.
As of year-end 2020, about 1,350 patients worldwide were receiving commercial ONPATTRO.
GIVLAARI (givosiran), a commercial-stage RNAi therapeutic for the treatment of adults with acute hepatic porphyria (AHP).

Preliminary global net product revenues for the fourth quarter and full year 2020 were approximately $22 million and $55 million, respectively.
These results represent greater than 30 percent quarter over quarter growth.
As of year-end 2020, the product’s first full year of launch, over 200 patients are receiving commercial drug.
OXLUMO (lumasiran), a commercial-stage RNAi therapeutic for the treatment of primary hyperoxaluria type 1 to lower urinary oxalate levels in pediatric and adult patients.

For the period following European Medicines Agency (EMA) and U.S. Food and Drug Administration (FDA) approval of OXLUMO, in late November 2020, strong initial U.S. demand was observed with 8 Start Forms received through year-end.
Preliminary global net product revenues for the fourth quarter were approximately $0.3 million representing initial patient demand in Europe
Finally, the Company today reported that it expects its full year 2020 non-GAAP operating loss to be substantially improved relative to the prior year, marking 2019 as Alnylam’s peak non-GAAP operating loss year as the Company transitions towards a self-sustainable financial profile.

Further, at December 31, 2020, Alnylam had preliminary cash, cash equivalents, and marketable securities of approximately $1.9 billion, as compared to $1.5 billion at December 31, 2019. The Company balance sheet was strengthened by the 2020 strategic financing collaboration with Blackstone.

"We are extremely pleased with ONPATTRO and GIVLAARI performance in the fourth quarter and cumulatively for the year, reflecting strong commercial execution, a substantial increase in demand and new patient adds, despite the ongoing COVID-19 pandemic. Additionally, we’re pleased to report that strong top-line revenue growth at the upper end of our guidance range and disciplined R&D and SG&A investments have delivered on a lower non-GAAP operating loss for 2020 compared with the prior year. We believe we’re now firmly on our way toward a self-sustainable financial profile with significant growth from four revenue generating assets and moderated operating expenses, and a balance sheet that supports achievement of profitability without the need to access the equity markets," said Jeff Poulton, Chief Financial Officer of Alnylam. "As we now launch our Alnylam P5x25 strategy, we’re committed to delivering consistently strong financial performance driven by 40% or greater revenue CAGR over the next five years with non-GAAP profitability achieved within the period."

Alnylam management will discuss these preliminary selected financial results and commercial updates during a webcast presentation at the 39th Annual J.P. Morgan Healthcare Conference tomorrow, Monday, January 11, 2021, at 8:20 a.m. ET.

About RNAi
RNAi (RNA interference) is a natural cellular process of gene silencing that represents one of the most promising and rapidly advancing frontiers in biology and drug development today. Its discovery has been heralded as "a major scientific breakthrough that happens once every decade or so," and was recognized with the award of the 2006 Nobel Prize for Physiology or Medicine. By harnessing the natural biological process of RNAi occurring in our cells, a new class of medicines, known as RNAi therapeutics, is now a reality. Small interfering RNA (siRNA), the molecules that mediate RNAi and comprise Alnylam’s RNAi therapeutic platform, function upstream of today’s medicines by potently silencing messenger RNA (mRNA) – the genetic precursors – that encode for disease-causing or disease pathway proteins, thus preventing them from being made. This is a revolutionary approach with the potential to transform the care of patients with genetic and other diseases.

On January 10, 2021 Istari Oncology, Inc., a clinical-stage biotechnology company, reported that the U.S. Food and Drug Administration (FDA) has granted orphan drug designation for PVSRIPO for the treatment of advanced melanoma (stage IIB-IV) (Press release, Istari Oncology, JAN 10, 2021, View Source [SID1234573789]). PVSRIPO is a novel viral immunotherapy, based on the Sabin type 1 polio vaccine, that activates a patient’s innate and adaptive immune system to facilitate an anti-tumor response and establish long-term immunologic memory to help prevent the cancer’s return.

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"We are happy to kick off the new year with the announcement that our request for an orphan drug designation has been granted to PVSRIPO for the treatment of advanced melanoma," said Matt Stober, President and Chief Executive Officer at Istari Oncology. "This is just one of many milestones to come in 2021 as we continue to drive the clinical development of PVSRIPO across multiple indications."

Currently, Istari is recruiting for LUMINOS-102, a Phase 2 open-label, randomized trial (clinicaltrials.gov NCT04577807) in patients with advanced, unresectable melanoma who previously failed anti-PD1 therapy. This study will characterize the safety, tolerability, and initial efficacy of PVSRIPO intratumoral injection alone and in combination with a PD-1 inhibitor. The first patient is expected to be dosed this quarter.

LUMINOS-102 follows a successful Phase 1 monotherapy study of PVSRIPO in anti-PD1 refractory advanced melanoma in which patients who received 3 injections (6/12) had an overall response rate of 67% (4/6).

"We are encouraged by the data from our Phase 1 trial presented at last year’s Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) 2020 annual meeting" said Garrett Nichols, MD, MS, Chief Medical Officer at Istari Oncology. "We plan to build upon that success with LUMINOS-102. As those data and the data from our other solid tumor trials emerge, we will continue to work closely with the FDA toward the goal of bringing PVSRIPO to market."

Melanoma is the deadliest type of skin cancer today with approximately 7,000 deaths in the U.S. each year. Treatment-resistant, advanced melanoma patients have very poor survival rates, with less than 28% of metastatic melanoma patients surviving 5 years1. PVSRIPO aims to address the significant unmet need in advanced melanoma, since most patients are treated with checkpoint inhibitors, and many do not respond or later become resistant and require other options, which are limited.

Orphan drug designation is granted by the FDA Office of Orphan Products Development (OOPD) to drugs or biological products intended for the treatment of rare diseases or conditions that impact fewer than 200,000 people in the U.S. This designation acts as a stimulus for the development of drugs for rare diseases through several incentives, including eligibility for federal grants, research and development tax credits, waiver of filing fees, and the potential for a seven-year marketing exclusivity period after FDA approval.

The granting of an orphan drug designation does not alter the standard regulatory requirements and process for obtaining marketing approval. More information about orphan drug designation can be found on the OOPD website.

For more information about Istari Oncology and their ongoing clinical trials, visit istarioncology.com.

About PVSRIPO
PVSRIPO is a virus based on the live attenuated Sabin type 1 polio vaccine that has been genetically modified for safety. Unlike other viral immunotherapies, PVSRIPO has a distinct target (the poliovirus receptor CD155), which is widely expressed in neoplastic cells of most solid tumors. Via CD155, PVSRIPO targets tumors with two primary mechanisms: 1) direct damage to and killing of cancerous cells; and 2) engaging innate and adaptive antitumor immune responses via sublethal infection of antigen presenting cells in the tumor, which unleashes an inflammatory cascade resulting in sustained systemic antitumor immunity. PVSRIPO has been granted Breakthrough Therapy Designation and Orphan Status by the FDA in recurrent glioblastoma. PVSRIPO has also been granted Orphan Status by the FDA for advanced melanoma.

About Melanoma
There are estimated to be over 12,000 new and recurrent cases of advanced, unresectable melanoma diagnosed in the U.S. each year, and around 7,000 deaths. While immune checkpoint inhibitors have dramatically improved the outlook for advanced melanoma patients today, most patients treated with these immunotherapies are either primary non-responders or eventually develop immune-refractory progressive disease and require additional therapy.

On January 10, 2021 Antengene Corporation Limited ("Antengene", SEHK: 6996.HK), a leading innovative biopharmaceutical company dedicated to discovering, developing and commercializing global first-in-class and/or best-in class therapeutics in hematology and oncology, reported that it will participate in the 39th Annual J.P. Morgan Healthcare Conference, which is the largest healthcare investment symposium in the industry (Press release, Antengene, JAN 10, 2021, View Source [SID1234573763]). Dr. Jay Mei, Founder, Chairman and CEO of Antengene, will present a corporate overview on Monday, January 11, 2021 at 8:40 a.m. EST (Monday, January 11, 2021 at 9:40 p.m. BJT).

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Antengene Corporation Limited (SEHK: 6996.HK)
Date: Monday, January 11
Time: 8:40 a.m. EST
Presenter: Dr. Jay Mei, M.D., Ph.D., Antengene’s founder, chairman and chief executive officer
Webcast: View Source;kiosk=true

On January 10, 2021 Sorrento Therapeutics, Inc. (Nasdaq: SRNE, "Sorrento"), reported that Dr. Henry Ji, Chairman and CEO, will participate in the following upcoming conference (Press release, Sorrento Therapeutics, JAN 10, 2021, View Source [SID1234573756]):

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H.C. WAINWRIGHT BIOCONNECT 2021 January 11-14, 2021 (Virtual Conference)
Sorrento’s Corporate Presentation will be available on-demand for 90 days starting on Monday, January 11, 2021 at 6:00 AM (Eastern Standard Time) at the following link:
View Source

An updated corporate presentation will also be available at www.sorrentotherapeutics.com.

On January 10, 2021 Exelixis, Inc. (Nasdaq: EXEL) reported its preliminary unaudited financial results for the fourth quarter and full year 2020, provided financial guidance for full year 2021, and delivered an update on its business (Press release, Exelixis, JAN 10, 2021, View Source [SID1234573754]). This 2021 financial guidance takes into consideration the anticipated U.S. Food and Drug Administration (FDA) approval and commercial launch of CABOMETYX (cabozantinib) in combination with OPDIVO (nivolumab) as a first-line treatment for patients with advanced renal cell carcinoma (RCC), which has a Prescription Drug Use Fee Act (PDUFA) target action date of February 20, 2021.

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Preliminary Fourth Quarter and Full Year 2020 Financial Results & 2021 Financial Guidance

The preliminary 2020 financial information presented in this press release has not been audited and is subject to change. The complete Exelixis Fourth Quarter and Full Year 2020 Financial Results are planned for release after market on Wednesday, February 10, 2021.

"2020 was a year of focused execution for Exelixis as we strengthened our foundation to potentially accelerate top-line revenue growth in 2021 and beyond. Throughout the year, the team advanced all of the components of our business and navigated the challenging COVID-19 pandemic environment to report data from late-stage trials, start new pivotal studies, ready next-generation Exelixis compounds for the clinic, and bring new assets and technologies into our pipeline," said Michael M. Morrissey, Ph.D., President and Chief Executive Officer of Exelixis. "We start 2021 with significant momentum as we prepare for the anticipated FDA approval of CABOMETYX in combination with OPDIVO based on the CheckMate -9ER trial. With the preliminary 2020 financial results announced today along with our 2021 guidance, we believe we are well positioned to deliver significant revenue growth throughout the new year and beyond as we capitalize on CABOMETYX’s future potential indications."

Dr. Morrissey continued: "In 2021 and beyond, we intend to pursue additional cabozantinib regulatory approvals and clinical development activities that unlock new treatment regimens, benefit a substantially greater number of patients and create the potential for a multi-billion-dollar franchise. CABOMETYX revenue directly supports our emerging pipeline of compounds with the potential to generate significant clinical and commercial value, including XL092, our improved next-generation oral, multi-targeted tyrosine kinase inhibitor that builds on our experience with cabozantinib. We expect to advance XL092 into pivotal trials in 2021 and believe it may ultimately become a source of long-term revenue for Exelixis. Additional programs are advancing alongside XL092, including XL102, our small molecule CDK7 inhibitor; XB002, our first antibody-drug conjugate; and multiple other programs. Overall, between our commercial, clinical, and pipeline activities, we are well on our way to becoming a multi-product oncology company that delivers on our mission to help cancer patients recover stronger and live longer."

Ahead of the company’s presentation at the J.P. Morgan Healthcare Conference tomorrow, Exelixis is also announcing its corporate priorities and anticipated key milestones for 2021, including potential supplemental New Drug Applications (sNDAs) for CABOMETYX, expanded clinical development activities for XL092, and multiple Investigational New Drug applications (INDs) for preclinical assets.

CABOMETYX and OPDIVO Combination for First-line Advanced RCC Represents Large and Growing Commercial Opportunity

In August 2020, Exelixis announced the submission of an sNDA to the FDA for CABOMETYX in combination with Bristol Myers Squibb’s (BMS) OPDIVO for patients with advanced RCC. In October 2020, Exelixis and BMS announced that the FDA had accepted each company’s regulatory application, granted Priority Review, and assigned a PDUFA goal date, or target action date, of February 20, 2021. Exelixis is ready to commercially launch this combination regimen in the United States, where an estimated 15,000 patients with advanced RCC are eligible for first-line treatment every year and with immune checkpoint inhibitor (ICI) combination therapy consisting of approximately 80% of that market. Based on the efficacy, safety and longer duration of therapy as observed in the CheckMate -9ER trial, Exelixis estimates that a doubling of CABOMETYX revenues in RCC alone may be achievable, with a potential $1.5 billion annualized run rate exiting 2022.
Potential sNDA Submissions for Cabozantinib in 2021

Relapsed radioiodine-refractory differentiated thyroid cancer (DTC): Exelixis expects to file an sNDA for the approval of cabozantinib monotherapy in patients with radioactive iodine-refractory DTC previously treated with a vascular endothelial growth factor receptor-targeted therapy. The sNDA will be based on the positive results from the phase 3 pivotal COSMIC-311 trial, which met its co-primary endpoint of progression-free survival (PFS) in December 2020.
Advanced hepatocellular carcinoma (HCC): Exelixis expects to report top-line data from COSMIC-312, a global phase 3 pivotal trial evaluating cabozantinib in combination with atezolizumab (TECENTRIQ), F. Hoffmann-La Roche Ltd.’s (Roche) anti-PD-L1 ICI, versus sorafenib in previously untreated advanced HCC, for the co-primary endpoints of PFS and overall survival (OS) in the first half of 2021. If the data are supportive, the company anticipates filing an sNDA in 2021, and its partner Ipsen Pharma SAS would also seek to file marketing applications with regulatory agencies in its respective territories based on the results. Exelixis completed enrollment in August 2020 for this global phase 3 pivotal trial. Separately, patient enrollment remains open in China in order to enroll a sufficient number of patients to potentially enable local registration.
Metastatic castration-resistant prostate cancer (CRPC): Should the data continue to be supportive, Exelixis anticipates filing an sNDA in 2021 seeking accelerated approval of cabozantinib in combination with atezolizumab, for the treatment of metastatic CRPC. A confirmatory phase 3 pivotal trial of this regimen in this patient population (CONTACT-02) was initiated in June 2020 under the clinical trial collaboration between Exelixis and Roche.
Additional Cabozantinib Clinical Updates

COSMIC-313: Exelixis expanded the enrollment target to 840 patients to provide additional power to assess the secondary endpoint of OS for COSMIC-313, the phase 3 pivotal trial evaluating the triplet combination of cabozantinib, nivolumab and ipilimumab (YERVOY) versus the combination of nivolumab and ipilimumab in patients with previously untreated advanced intermediate- or poor-risk RCC and expects to complete the expanded enrollment in early 2021. Top-line results of the event-driven analyses from the study are expected in 2022. If the data are supportive, the company would seek to file an sNDA with the FDA.
CONTACT trials: In 2020, as part of a clinical trial collaboration between Exelixis and Roche, three phase 3 global pivotal trials were initiated evaluating the combination of cabozantinib and atezolizumab: CONTACT-01 in patients with metastatic non-small cell lung cancer who have been previously treated with an ICI and platinum-containing chemotherapy; CONTACT-02 in patients with metastatic CRPC who have been previously treated with one novel hormonal therapy; and CONTACT-03, in patients with inoperable, locally advanced or metastatic RCC who progressed during or following treatment with an ICI.
Anticipated Progress for XL092 and Other Compounds Beginning Clinical Development in 2021

XL092: Exelixis is currently enrolling patients into the dose escalation cohorts of the phase 1b clinical trial of XL092 in combination with atezolizumab, and expects to initiate enrollment in the clear cell and non-clear cell RCC, hormone-receptor positive breast cancer and metastatic CRPC expansion cohorts shortly. The company also plans to initiate additional expansion cohorts in other tumor types, as well as potential additional studies, evaluating XL092 in combination with other oncology therapies, including ICIs. As data from these cohorts mature and are supportive, XL092 could enter pivotal trials over the course of 2021.
XL102: Following the FDA’s acceptance of its IND, Exelixis expects to initiate a phase 1 trial of XL102 (formerly known as AUR102), alone or in combination therapy for the treatment of inoperable, locally advanced or metastatic solid tumors. Exelixis in-licensed XL102 from Aurigene Discovery Technologies Limited in December 2020.
XB002: Exelixis anticipates beginning a phase 1 trial of XB002 (formerly known as ICON-2), in patients with inoperable, locally advanced or metastatic solid tumors. Exelixis in-licensed XB002 from Iconic Therapeutics, Inc. in December 2020 and plans to file an IND once the drug product release assays are finalized.
Additional INDs planned: Subject to preclinical data, Exelixis has the potential to file up to two additional INDs.
Presentation and Webcast

Exelixis President and Chief Executive Officer Michael M. Morrissey, Ph.D., will provide a corporate overview and discuss the company’s preliminary fourth quarter and full year 2020 financial results, 2021 financial guidance, and key priorities and milestones for 2021 during the company’s presentation at the J.P. Morgan Healthcare Conference beginning at 5:20 p.m. EST / 2:20 p.m. PST on Monday, January 11, 2021.

To access the webcast link, log onto www.exelixis.com and proceed to the News & Events / Event Calendar page under the Investors & Media heading. Please connect to the company’s website at least 15 minutes prior to the presentation to ensure adequate time for any software download that may be required to listen to the webcast. A replay will also be available at the same location for 90 days.