On December 7, 2021 AstraZeneca reported that it has entered into a new global development and commercialisation agreement with Ionis Pharmaceuticals, Inc. (Ionis) for eplontersen, formerly known as IONIS-TTR-LRX (Press release, AstraZeneca, DEC 7, 2021, View Source [SID1234596552]). Eplontersen is a ligand-conjugated antisense investigational medicine currently in Phase III clinical trials for amyloid transthyretin cardiomyopathy (ATTR-CM) and amyloid transthyretin polyneuropathy (ATTR-PN). It is designed to reduce the production of transthyretin (TTR protein) to treat both hereditary and non-hereditary forms of TTR amyloidosis (ATTR).

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The companies will jointly develop and commercialise eplontersen in the US, while AstraZeneca will develop and commercialise it in the rest of the world, except in Latin America.

ATTR-CM is a systemic, progressive and fatal condition that leads to progressive heart failure and death within four years from diagnosis.1 It remains underdiagnosed and its prevalence is thought to be underestimated due to a lack of disease awareness and the heterogeneity of symptoms.2 Hereditary ATTR-PN is a debilitating disease that leads to peripheral nerve damage with motor disability within five years of diagnosis and, without treatment, is generally fatal within a decade.3

Mene Pangalos, Executive Vice President, BioPharmaceuticals R&D, AstraZeneca, said: "Eplontersen has the potential to halt the progression of TTR-mediated amyloidosis, irrespective of whether it’s caused by genetic mutations or aging. Thanks to its precise liver-targeting properties, it also has the potential to be a best-in-class treatment for patients suffering from this devastating disease and who currently have limited options."

Hereditary ATTR-PN is expected to be the first indication for which the companies will seek regulatory approval for eplontersen, with the potential to file a new drug application with the US Food and Drug Administration by the end of 2022.

Financial considerations
AstraZeneca will pay Ionis an upfront payment of $200m and additional conditional payments of up to $485m following regulatory approvals. It will also pay up to $2.9bn of sales-related milestones based on sales thresholds between $500m and $6bn, plus royalties in the range of low double-digit to mid-twenties percentage depending on the region. The collaboration includes territory-specific development, commercial and medical affairs cost-sharing provisions.

The transaction will be funded with cash and is expected to be neutral to Core earnings in 2021. It will be accounted for as an intangible asset acquisition, recognised initially at the upfront amount, with any potential future milestone payments capitalised into the intangible asset as they are recognised.

Ionis will continue to manufacture and supply eplontersen for the existing clinical studies and process qualification. AstraZeneca will be responsible for commercial supply, with transition timing to be agreed by both parties. AstraZeneca will book all sales generated under the agreement.

The transaction is expected to close in the fourth quarter of 2021, subject to customary closing conditions and regulatory clearances. The transaction does not impact the AstraZeneca’s financial guidance for 2021.

Notes

Eplontersen
Eplontersen is a ligand-conjugated antisense (LICA) investigational medicine designed to reduce the production of transthyretin, or TTR protein, to treat all types of ATTR, a systemic, progressive and fatal disease.

TTR Amyloidosis (ATTR)
Cardiomyopathy and polyneuropathy due to ATTR are caused by aging or genetic mutations resulting in misfolded TTR protein and accumulation as amyloid fibrils in the cardiac myocardium and peripheral nerves, respectively. In patients with ATTR, both the mutant and wild type TTR protein builds up as fibrils in tissues, such as the peripheral nerves, heart, gastrointestinal system, eyes, kidneys, central nervous system, thyroid and bone marrow. The presence of TTR fibrils interferes with the normal functions of these tissues. As the TTR protein fibrils enlarge, more tissue damage occurs and the disease worsens, resulting in poor quality of life and eventually death. Worldwide, there are an estimated 300,000 – 500,000 patients with ATTR-CM4,5 and 10,000 – 40,000 patients with ATTR-PN2.

On December 7, 2021 HiberCell, a clinical-stage biotechnology company developing therapeutics to address therapeutic resistance, cancer relapse and metastasis, reported that it will present new data from the ongoing phase 2 open-label clinical trial evaluating the company’s odetiglucan (Imprime PGG), in combination with Merck’s anti-PD-1 therapy pembrolizumab, in patients with metastatic breast cancer at the 2021 San Antonio Breast Cancer Symposium (SABCS) from December 7-10, 2021 (Press release, HiberCell, DEC 7, 2021, View Source;utm_medium=rss&utm_campaign=hibercell-to-present-new-data-on-odetiglucan-plus-pembrolizumab-in-ongoing-phase-2-metastatic-breast-cancer-trial-at-san-antonio-breast-cancer-symposium [SID1234596551]).

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Odetiglucan is a Dectin-1, pattern recognition receptor agonist that has been observed to drive a coordinated innate and adaptive anti-cancer immune cell response in metastatic hormone receptor-positive, HER2-negative breast cancers (mBCA). Hibercell’s prior data supports its belief that combining odetiglucan with pembrolizumab will enhance mBCA patient sensitivity to checkpoint inhibitors (CPI) in those patients who have progressed through hormonal therapy with a CDK4/6 inhibitor. The World Health Organization assigned "odetiglucan" as the International Nonproprietary Name (INN) for Imprime PGG as of November 2021.

Odetiglucan plus pembrolizumab has shown encouraging results in preclinical studies and a prior phase 2 clinical trial, called IMPRIME 1. The ongoing phase 2 clinical trial is now recruiting patients at the SUNY Stony Brook Cancer Center, while actively opening additional clinical trial sites in the U.S.

Presentation number: OT1-18-05
Title: A Multicenter, Open-label, Phase 2 Study of Imprime PGG and Pembrolizumab in Patients with Metastatic Breast Cancer (mBCA) Who Have Progressed Through Prior Hormonal Therapy
Presenter: Alison Stopek, M.D., Stony Brook Cancer Center
Time/Date: Wednesday, December 8, 2021: 5:00 pm – 6:30 pm CT
For more information about HiberCell’s clinical trials, visit the website at www.HiberCell.com.

On December 7, 2021 Freenome, a privately held biotech company, reported a Series D funding of $300 million (Press release, Freenome, DEC 7, 2021, View Source [SID1234596550]). This brings the company’s total financing to over $800 million since the company was founded in 2014.

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This round of financing was led by investors Perceptive Advisors and RA Capital Management, joined by existing investors including a16z Life Sciences Growth Fund, the American Cancer Society’s BrightEdge Ventures, Artis Ventures, Bain Capital Life Sciences, Catalio Capital Management, Cormorant Capital, DCVC, Farallon Capital Management, Fidelity Management and Research Company LLC, GV, Janus Henderson Investors, Kaiser Permanente, Novartis, Polaris Partners, Ridgeback Capital Management, Roche Venture Fund, Rock Springs Capital, Sands Capital, Section 32, Soleus Capital Management, with funds and accounts advised by T. Rowe Price Associates, Inc.

In addition, there were several new biotech institutional investors well-placed to support the company’s mission including ArrowMark Partners, Byers Capital, Eventide Asset Management LLC, HBM Healthcare Investments, Intermountain Ventures, Logos Capital, Pura Vida Investments, Suvretta Capital Management, and other undisclosed funds.

The funding will support the advancement of the company’s colorectal cancer (CRC) screening test and expansion of its multiomics platform to other cancers. Freenome’s platform uses a routine blood test to detect cancer in its earliest stages, when it is most treatable.

It is estimated that nearly 53,000 people will die from CRC this year and only 67% of average-risk individuals over the age of 50 are up to date on CRC screening.¹ With recent guideline changes lowering the age from 50 to 45,² even more people need to be screened. Freenome’s multiomics blood test can help address adherence challenges with existing approaches by providing a convenient and patient-friendly option. The test is being validated in PREEMPT CRC, Freenome’s large, prospective registrational study, currently in the final stages of enrollment.

The company is also extending its platform to develop tests for other cancers and recently presented promising data in the detection of pancreatic cancer.

"We appreciate the shared belief our investors have in what is possible when it comes to fighting cancer," said Mike Nolan, chief executive officer of Freenome. "This funding gets us closer to bringing our early cancer detection tests to everyone, ultimately saving lives."

"We’re excited about Freenome’s multiomics platform and its ability to detect not just CRC but also other cancers," said Ellen Hukkelhoven, Ph.D., Perceptive Advisors. "We’re proud to help drive continued progress in bringing Freenome’s tests to the forefront of patient care."

"Freenome’s science backs up their mission, which is really exciting," said Peter Kolchinsky, Ph.D., RA Capital Management. "Detecting cancer when it is most treatable is critical to saving lives, and Freenome’s platform has demonstrated that’s possible."

On December 7, 2021 Recursion (NASDAQ: RXRX), a clinical-stage biotechnology company decoding biology to radically improve lives by industrializing drug discovery, development and beyond through disruptive innovation, reported a transformational collaboration with Roche (SIX: RO, ROG;OTCQX: RHHBY) and Genentech, a member of the Roche Group (Press release, Recursion Pharmaceuticals, DEC 7, 2021, View Source [SID1234596549]). Recursion will work with both Roche and Genentech’s R&D units to leverage technology-enabled drug discovery through the Recursion Operating System (OS) to more rapidly identify novel targets and advance medicines in key areas of neuroscience as well as in an oncology indication. Under the terms of the agreement, Recursion will receive an upfront payment of $150 million and is eligible for additional performance-based research milestones. Under the collaboration, Roche and Genentech (combined) may initiate up to 40 programs, each of which, if successfully developed and commercialized, could yield more than $300M in development, commercialization and net sales milestones for Recursion, as well as tiered royalties on net sales.

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The collaboration will leverage the Recursion OS, an integrated, multi-faceted system for generating, analyzing and deriving insight from massive proprietary biological and chemical datasets. The OS, which brings together wet-lab and dry-lab biology at scale to further industrialize and digitize drug discovery, will be deployed to phenomically capture chemical and genetic perturbations in neuroscience-related cell types and select cancer cell lines. The resulting phenomics data, generated in Recursion’s automated laboratories, will be analyzed by Recursion’s proprietary convolutional neural networks to turn these data into mathematical representations of biology that can be leveraged to identify novel biological relationships and initiate and advance therapeutic programs. This dataset will be potentiated by extensive single-cell perturbation screening data from Roche and Genentech, and the parties will collaborate on new machine learning algorithms to generate highly granular maps of human cellular biology.

"We are excited to partner with Roche and Genentech to bring Recursion’s leading-edge, tech-enabled drug discovery platform, the Recursion OS, to bear against some of the most complex diseases impacting humanity," said Recursion Co-Founder & CEO Chris Gibson, PhD. "Technology-enabled drug discovery is here, Recursion is leading the space, and we are pursuing some of the most intractable areas of biology with the very best partners by our side."

"This collaboration highlights the potential of technology to transform drug discovery and unlock previously unknown insights into complex disease in an unbiased way," said Global Head of Pharma Partnering at Roche, James Sabry, MD, PhD. "We are excited about the opportunity this collaboration offers to help advance the development of medicines at scale."

Recursion, Roche and Genentech will leverage the insights generated from the collaboration’s maps of human cellular biology to rapidly find and develop medicines against novel targets in neuroscience and the oncology indication for up to a decade or longer. Programs already underway at Recursion in oncology or neuroscience are not part of the collaboration and will be independently developed.

On December 7, 2021 Alvotech Holdings S.A. ("Alvotech"), a leading global biopharmaceutical company focused solely on the development and manufacture of biosimilar medicines for patients worldwide, and Oaktree Acquisition Corp. II (NYSE: OACB.U, OACB, OACB WS), a special purpose acquisition company sponsored by an affiliate of Oaktree Capital Management, L.P. ("Oaktree"), reported that they have entered into a definitive merger agreement. Upon completion of the transaction, the combined company’s securities are expected to be traded on NASDAQ under the symbol "ALVO (Press release, Alvotech, DEC 7, 2021, View Source [SID1234596548])."

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Company Overview

Alvotech, founded in 2013 in Reykjavik, Iceland, is a vertically integrated platform company focused exclusively on developing and manufacturing biosimilar medicines for the global market. Alvotech has a world class management team of proven and highly experienced pharmaceuticals executives with deep expertise in biologics and biosimilars, led by a visionary founder, Robert Wessman, who has a track record of building global biopharmaceutical companies.

Alvotech is dedicated to transforming patients’ lives by improving access to affordable biosimilar medicines and enhancing the sustainability of healthcare systems. A biosimilar medicine, offered at lower costs, is a biological product that is highly similar to and has no clinically meaningful difference from an existing approved biologic. Biologics are large complex molecules that have become the standard of care for many difficult-to-treat conditions. The global markets for biologic and biosimilar medicines have been rapidly growing over the last decade and are forecasted to grow at a 10%+ CAGR, reaching approximately $555 billion and approximately $80 billion by 2026, respectively1. By establishing the critical infrastructure needed to navigate the complexities inherent in developing biosimilar medicines at a global scale, Alvotech is uniquely positioned to succeed in the rapidly growing biosimilars market and to enable the global healthcare system to reduce the high cost of biologic medicines.

Alvotech aims to become a leading supplier of biosimilar medicines in all major markets around the world. To accomplish this objective, Alvotech has built a distinctive and comprehensive platform for developing and manufacturing biosimilars at scale over the past nine years with approximately $1 billion invested into the business to build critical elements of product development, including cell line development, process development and characterization, in addition to manufacturing, clinical development and conducting regulatory affairs, in-house to ensure the highest standards of product quality.

Alvotech currently has seven products in its pipeline across multiple therapeutic areas. Alvotech’s pipeline addresses originator products treating a diverse set of conditions across autoimmunity, ophthalmology, osteoporosis, and oncology, with total estimated peak originator sales of more than $80 billion combined.

Alvotech’s most advanced product is AVT02, the company’s biosimilar candidate to Humira. Humira is the world’s top selling pharmaceutical product with over $20 billion in global revenue in 2020. Alvotech was the first company to both file with the FDA for approval of its high-concentration adalimumab product and to have successfully conducted a switching study in support of an FDA designation of interchangeability. Alvotech’s other differentiated pipeline programs include biosimilar candidates to Stelara (ustekinumab), Eylea (aflibercept), Prolia/Xgeva (denosumab) and Simponi/Simponi ARIA (golimumab). In addition to its existing pipeline, Alvotech is also constantly evaluating new pipeline programs, both internally and through business development.

In order to give its products global reach, Alvotech has formed strategic commercialization partnerships covering 60+ countries with leading pharmaceutical companies. Alvotech’s partners, including Teva in the US and Stada in the EU, have licensed products in exchange for milestone payments and royalties. As of June 30, 2021, Alvotech had received license fee commitments of up to $1.15 billion under these partnerships, approximately 80% of which are still to be collected.

Management Comments

"We are delighted with this business combination and the long-term opportunities it will unlock for Alvotech," said Robert Wessman, Chairman and founder of Alvotech. "Through this important milestone, we believe that we are perfectly positioned to rapidly scale our portfolio with a like-minded partner who understands the intricacies of our business and our industry."

Howard Marks, Co-Chair of Oaktree, added, "Oaktree Acquisition Corp.’s strategy is guided by the same principles that are core to Oaktree’s broader investment philosophy, with a focus on long-term partnership and value creation. The Oaktree Acquisition Corp. franchise was formed to identify and partner with high-quality, growing companies that are making pivotal strides in their respective industries, and Alvotech is a clear fit with its meaningful contributions to sustainability within the healthcare ecosystem."

"Alvotech has built a highly attractive platform with a long-term view to lead the biosimilars market," said Zaid Pardesi, Managing Director at Oaktree and CFO & Head of M&A of Oaktree Acquisition Corp II. "The Company’s diverse pipeline and unique capabilities, in combination with its world-class distribution partners, set the stage for meaningful value creation and accelerated growth going forward."

Mark Levick, CEO of Alvotech, added, "Alvotech is in a unique position to impact the global healthcare ecosystem in a positive way and transform patient’s lives. Biosimilar medicines can increase access for patients whilst lowering cost for healthcare systems, and that helps to align our mission with all of our stakeholders. We believe this transaction will accelerate our ability to achieve our vision, and we could not be more excited about what the future holds for Alvotech."

Key Transaction Terms

The business combination is expected to deliver gross proceeds to Alvotech in excess of $450 million (assuming no redemptions). This includes cash proceeds of approximately $250 million from Oaktree Acquisition Corp. II’s trust account (assuming no redemptions); in excess of $150 million from private placement (PIPE) investors (the "PIPE Transaction"), including among others, funds managed by Suvretta Capital, Athos (the Strüngmann Family Office), CVC Capital Partners, Temasek, Farallon Capital Management, Sculptor Capital Management and premier Icelandic investors including Arctica Finance, Arion Bank, and Landsbankinn; and a $50 million equity commitment from existing shareholders to be funded prior to the end of 2021. The combined company will have an implied initial enterprise value of approximately $2.25 billion and will be well-positioned to continue investing in the growth of its biosimilar pipeline.

As part of the transaction, Alvotech’s existing equity holders have committed to roll 100% of their equity into the combined company. Leading existing institutional backers of Alvotech, including among others, Aztiq Pharma Partners, led by founder and Chairman Mr. Robert Wessman, Alvogen with CVC Capital Partners and Temasek as lead investors, Fuji Pharma from Japan, YAS Holdings from Abu Dhabi, Shinhan from Korea, Baxter Healthcare SA from the US, and Athos (the Strüngmann Family Office) from Germany intend to roll 100% of their shares into the combined company. Assuming no public shareholders of Oaktree Acquisition Corp. II exercise their redemption rights, current Alvotech equity holders will own approximately 80%, Oaktree Acquisition Corp. II shareholders will own approximately 11%, and PIPE investors will own approximately 7% of the issued and outstanding ordinary shares, respectively, of the combined company at closing.

The transaction also includes earn-out provisions tied to the trading price of the combined company’s shares, reflecting an alignment of interest with shareholders. Oaktree Acquisition Corp. II’s sponsor is deferring 1.25 million founder shares into an earn-out at share price hurdles of $12.50 and $15.00. The transaction also includes an earn-out to existing shareholders of Alvotech, consisting of 38.3 million shares, which will vest evenly at share price hurdles of $15.00 and $20.00.

The transaction, which has been unanimously approved by the boards of directors of each Alvotech and Oaktree Acquisition Corp. II, is subject to, among other customary closing conditions, approval by shareholders of Oaktree Acquisition Corp. II, and shareholders of Alvotech, with the holders of a majority of the votes required to approve the transaction having provided commitments to approve the transaction. The transaction is expected to close in the first half of 2022.

A more detailed description of the transaction terms and a copy of the Business Combination Agreement will be included in a current report on Form 8-K to be filed by Oaktree Acquisition Corp. II with the United States Securities and Exchange Commission (the "SEC"). Oaktree Acquisition Corp. II will file a registration statement (which will contain a proxy statement/ prospectus) with the SEC in connection with the transaction.

Advisors

Morgan Stanley & Co. LLC and Credit Suisse served as financial advisors to Alvotech. Deutsche Bank Securities served as financial advisor and capital markets advisor to Oaktree Acquisition Corp. II. Deutsche Bank Securities and Morgan Stanley & Co. LLC served as lead private placement agents, and Citigroup Global Markets Inc. and Credit Suisse also served as private placement agents, for Oaktree Acquisition Corp. II in connection with the PIPE Transaction. Cooley (UK) LLP served as lead legal counsel to Alvotech. Kirkland and Ellis LLP and King & Spalding served as legal counsel to Oaktree Acquisition Corp. II. Shearman & Sterling LLP served as legal counsel to the placement agents.

Management Presentation

A presentation made by the management teams each of Alvotech and Oaktree Acquisition Corp. II regarding the transaction will be available on the websites of Oaktree Acquisition Corp. II at View Source and Alvotech at View Source Oaktree Acquisition Corp. II will also file the presentation and transcript of related remarks with the SEC as an exhibit to a Current Report on Form 8-K, which can be viewed on the SEC’s website at www.sec.gov.