On July 14, 2021 Eli Lilly and Company (NYSE: LLY) reported the acquisition of Protomer Technologies ("Protomer"), a private biotech company (Press release, Eli Lilly, JUL 14, 2021, View Source [SID1234584832]). Protomer’s proprietary peptide- and protein-engineering platform is used to identify and synthesize molecules that can sense glucose or other endogenous modulators of protein activity.

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The potential value of the transaction is over $1 billion, with successful achievement of future development and commercial milestones. Lilly previously led an equity investment in Protomer alongside the JDRF T1D Fund, providing Lilly with 14 percent ownership of the company. Lilly is acquiring the remainder of the stock of Protomer beyond its initial investment.

Founded in 2015 and based in Pasadena, California, Protomer is engineering next-generation protein therapeutics that can sense molecular activators in the body. The company’s proprietary chemical biology-based platform enables the development of therapeutic peptides and proteins with tunable activity that can be controlled using small molecules. Protomer has used this approach toward advancing a portfolio of therapeutic candidates, including glucose-responsive insulins that can sense sugar levels in the blood and automatically activate as needed throughout the day.

"Lilly has long strived to make life better for people living with diabetes and we have a continued determination to provide real solutions, including innovation in insulin therapy. Glucose-sensing insulin is the next frontier and has the potential to revolutionize the treatment and quality of life of people with diabetes by dramatically improving both therapeutic efficacy and safety of insulin therapy," said Ruth Gimeno, vice president, diabetes research and clinical investigation at Lilly. "Protomer’s glucose-sensing insulin program, based on its proprietary molecular engineering of protein sensors (MEPS) platform, is showing significant promise and Lilly is excited to enhance our diabetes pipeline with the company’s innovative technology."

"We are excited to join Lilly, a leader in diabetes therapies, and advance our science with their support to better serve the needs of patients. This transaction validates our team’s accomplishments, and we look forward to continuing our important work together with Lilly," said Alborz Mahdavi, CEO and founder of Protomer. "We have been supported by JDRF since our inception and working closely with one of the leading organizations in type 1 diabetes research has been invaluable for us. The Protomer team is excited to embark on the next chapter of our work at Lilly as we focus our efforts on advancing glucose-responsive insulins and accelerating the development of these next-generation protein therapeutics."

"This is a significant milestone for the T1D community and a key step to bring the promise of Protomer’s game-changing technology one step closer to the clinic," said Katie Ellias, managing director at the JDRF T1D Fund. "Our early support and investment in Protomer is emblematic of our Fund’s mission to help companies with novel science accelerate next generation life-changing therapies for people living with T1D. We are thrilled Protomer has found a home at Lilly, a company that shares our commitment to delivering solutions to the diabetes community."

This transaction will be reflected in Lilly’s reported results and financial guidance according to Generally Accepted Accounting Principles (GAAP). There will be no change to Lilly’s 2021 non-GAAP earnings per share guidance as a result of this transaction.

Aquilo Partners, L.P. is acting as financial advisor and Morrison & Foerster LLP as legal advisor to Protomer. Kirkland & Ellis LLP is serving as Lilly’s legal counsel.

On July 13, 2021 Evrys Bio, a biotech company developing Next Gen Antivirals, reported the company was awarded a $34.3 million contract from the Department of Defense (DOD) to develop a drug, simultaneously effective against multiple high-risk viral agents (Press release, Evrys Bio, JUL 13, 2021, View Source [SID1234644911]). The proposed drug intends to improve disease survival after exposure to one or more viruses from three families: alphaviruses, arenaviruses and filoviruses. Evrys Bio’s broad-spectrum antiviral technology is based on the discovery that certain human proteins, called sirtuins, normally defend the human (host) cell from being invaded by pathogens. The novel drug will target the human SIRT-2 protein.

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The DOD’s Defense Threat Reduction Agency’s Chem Bio Technologies, Vaccines and Therapeutics Division executed an Other Transaction Authority (OTA) agreement with Evrys for this effort. The milestone-based agreement anticipates five years of development from drug-prototype identification to proof-of-concept and regulatory filings.

"EVRYS stands for the Company’s vision to ultimately address every virus," said Lillian Chiang, PhD, CEO, Evrys Bio. "This DTRA collaboration addresses highly lethal viral infection and extends our pipeline that already includes developing products to treat pan-respiratory, pan-hepatic, and pan-opportunistic viral infections."

On July 13, 2021 Prime Medicine, a company delivering on the promise of Prime Editing to provide lifelong cures to patients, reported its launch with $315 million in financing (Press release, Prime Medicine, JUL 13, 2021, View Source [SID1234621403]).

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The financing comprised a $115 million Series A; based on the rapid progress of the science and the company, Prime Medicine expanded its syndicate support with a $200M Series B financing approximately nine months after the company began operations. Investors in the Series A included ARCH Venture Partners, F-Prime Capital, GV, and Newpath Partners. The Series B included all Series A investors, plus Casdin Capital, Cormorant Asset Management, Moore Strategic Ventures, Public Sector Pension Investment Board (PSP Investments), Redmile Group, Samsara BioCapital, funds and accounts advised by T. Rowe Price Associates, Inc., and a number of additional, unnamed life sciences investment funds.

"Prime Editing is a wonderful example of the revolution in genetic medicine that we are living through," said Robert Nelsen, co-founder and Managing Director of ARCH Venture Partners. "When mature, gene editing technologies like this could totally change our conception of what’s possible in treating disease."

"This is an opportunity to take a giant step toward cures for a much wider range of diseases than previously possible," said Stephen Knight, MD, President and Managing Partner of F-Prime Capital.

The funds raised will be used to continue building the company, rapidly advance towards clinical indications, expand the capabilities of the platform, and to further enhance the exceptional promise of Prime Editing. By the end of 2021, Prime Medicine expects to employ more than 100 people full-time.

"Prime Editing represents an opportunity to do what no gene editing approach has yet been capable of – correcting nearly all types of pathogenic gene mutations, correcting multiple mutations at once, and bringing durable cures to patients across multiple disease areas, potentially with a single ‘once and done’ treatment approach," said David Schenkein, MD, General Partner at GV. "We are tremendously excited about the potential of this technology, and about the talented team at Prime working to bring it to patients."

Prime Editing is a next-generation gene editing technology that acts like a DNA word processor to "search and replace" disease-causing genetic sequences at their precise location in the genome, without resulting in double-strand DNA breaks that cause unwanted cellular changes. It is versatile, with the potential to address more than 90 percent of known disease-causing mutations, and works in a variety of dividing and non-dividing primary human cells, as well as in animals. Prime editing has been shown by multiple independent laboratories to make genome edits with high fidelity, making edits precisely at the desired location with minimal or no editing in other parts of the genome. Together, these features overcome several technical barriers attributed to earlier gene editing technologies.

"Prime Editing is a transformative technology that we believe will make a significant impact by addressing the fundamental causes of genetic disease," said Keith Gottesdiener, MD, CEO of Prime Medicine. "Since Prime began operations in the summer of 2020, we have continued to make great progress in advancing the performance of Prime Editing, which allowed us to close our Series B financing nine months later. We are operating from a position of financial strength, and look forward to further developing the technology and progressing our preclinical programs toward the clinic, with the hope that they may cure or halt the progression of genetic diseases for patients."

On July 13, 2021 Cellectar Biosciences, Inc. (NASDAQ: CLRB), a late-stage clinical biopharmaceutical company focused on the discovery and development of drugs for the treatment of cancer, reported that it has expanded its ongoing collaboration with IntoCell Inc., a biotechnology company based in South Korea (Press release, Cellectar Biosciences, JUL 13, 2021, View Source [SID1234612852]).

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The parties have been collaborating on combining IntoCell’s validated novel Ortho-Hydroxy Protected Aryl Sulfate (OHPAS) linker chemistry with Cellectar’s validated novel targeting platform, phospholipid ethers (PLEs) to develop new PDCs. IntoCell’s platform significantly enhances the utility of traditional antibody drug conjugate linkers by customizing the entire linker to a specific project. The collaboration has exceeded the necessary preclinical results to warrant further development and the initiation of Investigational New Drug (IND) enabling studies with multiple payloads. Cellectar will have the right to globally develop and commercialize any OHPAS containing PDC.

"Since initiating our multi-target collaboration, Cellectar has been able to advance various PDC candidates which leverage the differentiated advantages of IntoCell’s technology," said James Caruso, president and CEO of Cellectar. "Through this arrangement we are excited to broaden our research into next-generation targeted therapies and anticipate the development of additional candidates for Cellectar’s growing small molecule PDC pipeline."

"We have built a strong partnership with Cellectar through the multi-target PDC platform collaboration. Our partnership has validated the use of PLEs with our novel OHPAS linker platform technology and the competitive potential of these innovative PDCs. This validation has led to the expansion of our collaboration," said Tae Kyo Park, Founder and CEO of IntoCell. "We will continue to cooperate closely with Cellectar to accelerate the advancement of IntoCell-related PDC candidates into clinical trials."

About IntoCell and the OHPAS linker
IntoCell is a Korea-based biotechnology company dedicated to the development and commercialisation of novel antibody drug conjugate (ADC) platform technologies comprising scaffold moiety, ligands, toxins, linkers and conjugation methods. IntoCell has developed a novel self-immolative Ortho-Hydroxy Protected Aryl Sulfate (OHPAS) linker that works with a wide variety of functional groups, triggering groups, and both phenolic and non-phenolic payloads. The resulting ADCs have proven to be highly stable in chemical and biological environments and have demonstrated excellent potencies in-vitro and in-vivo. IntoCell has also developed proprietary benzodiazepine dimers and modified duocarmycinoids that show high potency with improved safety in preclinical models. IntoCell has created an OHPAS Linker-toxin Library containing a variety of toxins that can be optimized for the fast delivery of a pre-clinical candidate in novel ADC programs.

Using its novel chemistries, IntoCell is developing a pipeline of proprietary ADCs that includes a B7-H3 programme which is demonstrating excellent preclinical data.

For more information, please visit View Source

On July 13, 2021 HUTCHMED (China) Limited ("HUTCHMED") (Nasdaq/AIM: HCM; HKEX: 13) reported the first commercial sale in China of ORPATHYS (savolitinib), HUTCHMED’s oral, potent, and highly selective small molecule inhibitor of MET, a receptor tyrosine kinase, which occurred on July 12, 2021 (Press release, Hutchison China MediTech, JUL 13, 2021, https://www.hutch-med.com/first-commercial-sale-of-orpathys-milestone-payment/ [SID1234586916]).

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This follows less than three weeks after the June 22, 2021 approval of ORPATHYS in China for the treatment of patients with locally advanced or metastatic non-small cell lung cancer ("NSCLC") with MET exon 14 skipping alterations who have progressed following prior systemic therapy or are unable to receive chemotherapy.

Under the terms of the license and collaboration agreement between HUTCHMED and AstraZeneca ("AstraZeneca") (LSE/STO/Nasdaq: AZN), a US$25 million non-creditable and non-refundable milestone payment is triggered by the first commercial sales of ORPATHYS in China. HUTCHMED is responsible for the clinical development, marketing authorization, manufacturing and supply of ORPATHYS in China, while AstraZeneca is responsible for its commercialization for which it will pay HUTCHMED fixed royalties of 30% based on all China sales.

More than a third of the world’s lung cancer patients are in China and, among those with NSCLC, approximately 2-3% have tumors with MET exon 14 skipping alterations, a targetable mutation in the MET gene.[i],[ii],[iii] This mutation is more common (13-22%) among patients with pulmonary sarcomatoid carcinoma (PSC), a rare and aggressive subtype of NSCLC usually resistant to chemotherapy.[i],[iv]

About ORPATHYS
ORPATHYS is an oral, potent, and highly selective MET tyrosine kinase inhibitor ("TKI") that has demonstrated clinical activity in advanced solid tumors. It blocks atypical activation of the MET receptor tyrosine kinase pathway that occurs because of mutations (such as exon 14 skipping alterations or other point mutations) or gene amplification.

ORPATHYS is marketed in China for the treatment of patients with NSCLC with MET exon 14 skipping alterations who have progressed following prior systemic therapy or are unable to receive chemotherapy. It is currently under clinical development for multiple tumor types, including lung, kidney, and gastric cancers, as a single treatment and in combination with other medicines.

ORPATHYS development in NSCLC
Phase II study of ORPATHYS monotherapy in MET Exon 14 skipping alteration NSCLC (NCT02897479) – In June 2021, ORPATHYS was granted drug registration conditional approval by the National Medical Products Administration of China (NMPA) for MET Exon 14 skipping alteration NSCLC. The approval was based on the results of a Phase II study in China; results of this study were presented during the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) ASCO (Free ASCO Whitepaper)20 Virtual Scientific Program in May 2020, and updated results were published in The Lancet Respiratory Medicine in June 2021. At a median follow up of 17.6 months, ORPATHYS demonstrated an objective response rate ("ORR") of 42.9% (95% confidence interval [CI] 31.1-55.3) and median progression-free survival ("PFS") of 6.8 months (95% CI 4.2-9.6) in the overall trial population. PFS was clinically meaningful across subgroups, and ORR results were consistent regardless of prior treatment or tumor histology, including in patients with the PSC subtype (40.0%, 95% CI 21.1-61.3) and patients with other NSCLC subtypes (44.4%, 95% CI 29.6-60.0). Disease control rate ("DCR") in the overall trial population was 82.9% (95% CI 72.0-90.8). The safety and tolerability profile of ORPATHYS was consistent with previous trials, and no new safety signals were identified.

SAVANNAH Phase II study of ORPATHYS in combination with TAGRISSO in patients who have progressed following TAGRISSO due to MET amplification or overexpression (NCT03778229) – This is a single-arm, open-label, global study in epidermal growth factor receptor ("EGFR") mutation positive NSCLC patients with MET amplified/overexpressed tumors following progression after treatment with TAGRISSO, an EGFR TKI owned by AstraZeneca.

Phase III study of ORPATHYS in combination with TAGRISSO in patients who have progressed following EGFR TKI treatment due to MET amplification (in planning) – This is a randomized, open-label study in China in EGFR mutation positive NSCLC patients with MET amplified tumors following progression after treatment with any EGFR TKI.

Phase III study of ORPATHYS in combination with TAGRISSO in treatment naïve patients with EGFR mutant positive NSCLC with MET overexpression (in planning) – This is a randomized, blinded study in China in untreated, unresectable or metastatic patients with EGFR mutation positive NSCLC with MET positive tumors.

ORPATHYS development in kidney cancer
SAVOIR randomized, controlled study of ORPATHYS monotherapy in MET-driven papillary renal cell carcinoma ("RCC") (NCT03091192) – In May 2020, data from 60 patients in this global study of ORPATHYS monotherapy compared with sunitinib monotherapy in MET-driven papillary RCC was presented at the ASCO (Free ASCO Whitepaper) 2020 Program and published simultaneously in JAMA Oncology. ORPATHYS demonstrated encouraging activity, including an ORR of 27% versus 7% for sunitinib, with no ORPATHYS responding patients experiencing disease progression at data cut-off, and an encouraging overall survival ("OS") hazard ratio of 0.51 (95% CI: 0.21–1.17; p=0.110) with median not reached at data cut-off.

CALYPSO Phase I/II study of ORPATHYS in combination with IMFINZI PD-L1 inhibitor in RCC (NCT02819596) – The CALYPSO study is an investigator initiated open-label Phase I/II study of ORPATHYS in combination with IMFINZI, a PD-L1 antibody owned by AstraZeneca. The study is evaluating the safety and efficacy of the ORPATHYS/IMFINZI combination in patients with papillary RCC and clear cell RCC. An analysis of 41 patients enrolled in the PRCC cohort of in this study was presented at the 2021 ASCO (Free ASCO Whitepaper) Annual Meeting, showing a confirmed response rate in 14 MET-driven patients of 57%, with a median duration of response ("DoR") of 9.4 months, median PFS of 10.5 months and median OS of 27.4 months. No new safety signals were seen.

Phase III in combination with IMFINZI PD-L1 inhibitor in MET-driven, unresectable and locally advanced or metastatic PRCC (in planning) – Based on the encouraging results of the SAVOIR and CALYPSO studies, we intend to initiate a global Phase III, open-label, randomized, controlled study of ORPATHYS plus IMFINZI versus sunitinib monotherapy versus IMFINZI monotherapy in patients with MET-driven, unresectable and locally advanced or metastatic PRCC.

ORPATHYS development in other cancer indications
Phase II study of ORPATHYS monotherapy in advanced or metastatic MET amplified gastric cancer ("GC") or adenocarcinoma of the gastroesophageal junction ("GEJ") (NCT04923932) – This Phase II trial is an open-label, two-cohort, multi-center study to evaluate the efficacy, safety and pharmacokinetics ("PK") of ORPATHYS in locally advanced or metastatic GC or GEJ patients whose disease progressed after at least one line of standard therapy. The primary endpoint is ORR as assessed by an independent review committee. Other endpoints include 12-week and 6-month PFS rates, median PFS, DoR, DCR, median OS, safety, PK and quality of life.

This trial follows multiple Phase II studies that have been conducted in Asia to study ORPATHYS in MET-driven gastric cancer patients, including VIKTORY.[v] VIKTORY is an investigator initiated Phase II umbrella study in gastric cancer in South Korea in which a total of 715 patients were successfully sequenced into molecular-driven patient groups, including those with MET amplified gastric cancer. Patients whose tumors harbor MET amplification were treated with ORPATHYS monotherapy, reporting an ORR of 50% (10/20, 95% CI: 28.0, 71.9).

ORPATHYS opportunities are also continuing to be explored in multiple other MET-driven tumor settings via investigator-initiated studies including non-small cell lung cancer, gastric cancer and colorectal cancer.