On December 7, 2021 Greenwich LifeSciences, Inc. (Nasdaq: GLSI) (the "Company"), a clinical-stage biopharmaceutical company focused on the development of GP2, an immunotherapy to prevent breast cancer recurrences in patients who have previously undergone surgery, reported the expansion of Dr. F. Joseph Daugherty’s role to include the critical responsibility of Medical Monitor of the Phase III clinical trial and a long-term agreement to serve as Chief Medical Officer (Press release, Greenwich LifeSciences, DEC 7, 2021, View Source [SID1234596563]).

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Dr. Daugherty commented, "I look forward to supporting the GLSI-100 clinical trials as Medical Monitor. While GP2 has been shown to be both effective and safe in the Phase IIb trial, we will maintain our vigilance in the larger Phase III trial. The mild local and systemic reactions observed in the Phase IIb trial have served to further validate the immune response and mechanism of action of GP2, thus requiring the balancing of dosing to ensure that local and systemic reactions are tolerable and safe, yet still sufficiently robust enough to lead to the prevention of metastatic breast cancer recurrence."

CEO Snehal Patel added, "We are very excited that Dr. Daugherty is expanding his role with a very significant commitment to serve as medical monitor of our upcoming and future clinical trials as we seek to expand GP2’s potential to all HER2 positive breast cancer patients and to explore HER2 low breast cancer and other HER2 expressing cancers. While we have not seen any serious adverse events in the 138 patients we have treated to date across four clinical trials attributable to GP2 immunotherapy, Dr. Daugherty’s responsibility to oversee the safety of our Phase III trial will be a key component of our regulatory strategy in this potential single registration trial."

Dr. Daugherty has over 40 years of experience in managing and overseeing biotechnology and biomedical projects. He served first as President and recently as Chief Executive Officer, Chief Medical Officer, and the Chairman of the board of directors of Eleos, Inc., a clinical-stage, private biotech company focused on anti-sense technology in hematologic cancers. In addition to being an officer and director, Dr. Daugherty has served in various other capacities, including as a management consultant to over 20 public and private biomedical companies including Dupont, Inc, and as President of ConAgra’s biotech division. He received a BA in Biology from Washington University, a MD from the University of Nebraska, and a MS in Industrial Administration from Carnegie Mellon University.

About FLAMINGO-01 and GLSI-100

The Phase III clinical trial will be called FLAMINGO-01 and the combination of GP2 + GM-CSF will be called GLSI-100. The Phase III trial is comprised of 2 blinded, randomized, placebo-controlled arms for approximately 500 HLA-A*02 patients and 1 open label arm of up to 100 patients for all other HLA types. An interim analysis has been designed to detect a hazard ratio of 0.3 in IDFS, where 28 events will be required. An interim analysis for superiority and futility will be conducted when at least half of those events, 14, have occurred. This sample size provides 80% power if the annual rate of events in placebo-treated subjects is 2.4% or greater. The trial is currently being registered on clinicaltrials.gov and the link and trial identifier will be published shortly. For future updates about FLAMINGO-01 please visit the Company’s clinical trial tab at View Source

About Breast Cancer and HER2/neu Positivity

One in eight U.S. women will develop invasive breast cancer over her lifetime, with approximately 282,000 new breast cancer patients and 3.8 million breast cancer survivors in 2021. HER2/neu (human epidermal growth factor receptor 2) protein is a cell surface receptor protein that is expressed in a variety of common cancers, including in 75% of breast cancers at low (1+), intermediate (2+), and high (3+ or over-expressor) levels.

On December 7, 2021 Privo Technologies, Inc. ("Privo"), a biopharmaceutical company focused on optimizing state-of-the-art chemotherapies to be "Tough on cancer, Easy on patients", reported that the Company will be attending the virtual Biotech Showcase from January 17 to January 19, 2022 (Press release, Privo Technologies, DEC 7, 2021, View Source;utm_medium=rss&utm_campaign=privo-technologies-inc-to-attend-biotech-showcase-2022 [SID1234596547]). Members of Privo’s management team will be available for 1×1 meetings with interested parties. Those registered for the event can request a meeting with Privo through the partneringOne portal.

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On December 7, 2021 SynDevRx, Inc., a clinical-stage biotechnology company leading the development in treatments for obesity-accelerated cancers, reported a research collaboration with Australia’s Queensland University of Technology (Press release, SynDevRx, DEC 7, 2021, View Source [SID1234596566]). The collaboration with Professor Colleen Nelson, PhD, and her team will study the role of methionine aminopeptidase 2 (MetAP2) inhibition in tumor growth in castration resistant and other treatment resistant forms of prostate cancer.

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Obesity and systemic metabolic dysfunction like pre-diabetes and type 2 diabetes are known to make many solid tumors more aggressive, including prostate cancer. MetAP2 inhibitors, such as evexomostat (SDX-7320), have been clinically shown to improve systemic metabolic hormone dysregulation1 and to possess direct anti-tumor, anti-metastatic and anti-angiogenic properties2. This combination of attributes may be well suited to sever the link between metabolic dysfunction and cancer, and may prove to be effective in treating advanced prostate cancer in combination with standard-of-care therapies.

Professor Nelson is the founder and executive director of the Australian Prostate Cancer Research Centre – Queensland (APCRC-Q) and Chair of Prostate Cancer Research at Queensland University of Technology (QUT). APCRC-Q, is one of the leading global research facilities investigating the connection between prostate cancer and dysregulated metabolic hormones and pathways, and how these affect prostate cancer progression and metastasis. "The downstream effects of obesity change the tumor microenvironment in ways highly favorable to prostate cancer recurrence, progression and metastasis. Hyperleptinemia and hyperinsulinemia are well-established, negative side effects of androgen deprivation therapy (ADT) and other treatments that block the androgen axis in prostate cancer. The APCRC-Q has been investigating this relationship using targeted drugs in preclinical models that inhibit metabolic pathways induced by ADT, through tumor promoting pathways activated systemically, and through direct tumor cell adaptation," said Colleen Nelson, PhD, lead investigator. "We’re very excited to study SynDevRx’s SDX-7320 inhibition of MetAP2 in our well-vetted models of treatment resistant advanced prostate cancer models."

The APCRC-Q team’s research focuses on pathways activated by ADT, including alterations in metabolism that are druggable with novel targeted agents. They recently showed that pharmacological blockade of leptin receptor or the activation of adiponectin signaling was efficacious in significantly reducing tumor burden and in delaying progression to castration resistance in animal models. The APCRC-Q team has also been targeting metabolic pathways directly through mitochondrial activity or lipid synthesis in models of CRCP and ENZ resistance.

"Professor Nelson team’s work has clearly demonstrated the central role that leptin and adiponectin play in the feedback loop of androgen deprivation and results in the emergence of treatment resistance," said Peter Cornelius, PhD, senior director of translational research at SynDevRx. "Her lab has some of the best models for studying the deleterious effects of inhibition of the androgen receptor axis in prostate cancer, identifying mechanisms of resistance and then targeting those proteins driving the resistance in pre-clinical prostate cancer models. Given our clinical results showing evexomostat (SDX-7320) significantly lowers leptin and increases adiponectin in late-stage cancer patients, we’re thrilled to work with Professor Nelson and her expert team on testing the potential beneficial effects that SDX-7320/MetAP2 inhibition could play in these validated models."

"SynDevRx is establishing global collaborations with leading research institutions focused on the downstream effects that obesity and dysregulated metabolic hormones have on cancer progression and metastasis. We invite other researchers to work with us as we untangle these complex and critical interactions between cancer and dysregulated metabolic hormones," said SynDevRx’s co-founder and Chief Business Officer James Shanahan.

(Proietto et al., Diabetologia 2018 Sep;61(9):1918-1922)
(Mann-Steinberg et al., "TNP-470: The Resurrection of the First Synthetic Angiogenesis Inhibitor." (2008).)
About SDX-7320

SynDevRx believes that evexomostat (SDX-7320) is the first drug being developed specifically for cancer patients with metabolic complications, such as obesity, diabetes, high blood glucose or HbA1c, pre-diabetes or insulin/leptin resistance. For certain tumor types, metabolic hormones stimulate oncogenic pathways, making the cancer more aggressive and deadlier. Evexomostat acts by binding irreversibly to its target enzyme MetAP2, triggering downstream improvements in the metabolic hormones insulin, leptin and adiponectin, improvements in key lipids, and inhibition of the important angiogenic proteins bFGF and VEGF-C, as was demonstrated in a Phase 1 clinical study in late-stage cancer patients. In preclinical studies, evexomostat also directly inhibited multiple cell cycle signaling pathways, provided synergistic anti-tumor effects in combination with a PI3K inhibitor, reduced angiogenesis, controlled aberrant metabolic hormone signaling, and reversed obesity-induced immune suppression within the tumor micro-environment of tumor-bearing obese mice. Evexomostat (SDX-7320) is being developed for use in combination with clinically indicated standard-of-care cancer therapies for breast and prostate cancers.

On December 7, 2021 METiS Therapeutics reported the company debut with $86 million Series A financing to harness artificial intelligence (AI) and machine learning to redefine drug discovery and delivery and develop optimal therapies for patients with serious diseases (Press release, METiS Therapeutics, DEC 7, 2021, View Source [SID1234648428]). PICC PE and China Life led the financing and were joined by Sequoia Capital China, Lightspeed, 5Y Capital, FreeS Fund and CMBI Zhaoxin Wuji Fund. The financing will be used to advance the company’s pipeline of novel assets with high therapeutic potential and the continued development of its AI-driven drug discovery and delivery platform.

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"METiS is well-positioned to change the drug discovery and delivery landscape with the creation of a proprietary predictive AI platform. We leverage machine learning, AI and quantum simulation to uncover novel drug candidates and to transform drug discovery and development, ultimately bringing the best therapies to patients in need," said Chris Lai, CEO, and Founder, METiS Therapeutics. "We are fortunate that our world-class roster of investors believes in our vision and today’s news represents the first of many significant milestones that we will be accomplishing throughout the next year."

The METiS platform (AiTEM) combines state-of-the-art AI data-driven algorithms, mechanismdriven quantum mechanics and molecular dynamics simulations to calculate Active Pharmaceutical Ingredient (API) properties, elucidate API-target and API-excipient interactions, and predict chemical, physical and pharmacokinetic properties of small molecule and nucleic acid therapeutics in specific microenvironments. This enables efficient lead optimization, candidate selection and formulation design. Founded by a team of MIT researchers, serial entrepreneurs and biotech industry veterans, METiS develops and in-licenses novel assets with high therapeutic potential that could benefit from its data-driven platform.

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.