On October 19, 2022 PIC Therapeutics, Inc., a biopharmaceutical company dedicated to developing life-changing medicines for patients with cancer, reported the closing of a $35 million Series A financing led by OrbiMed (Press release, PIC Therapeutics, OCT 19, 2022, View Source [SID1234622183]). Other new investors participating in this financing include Lumira Ventures and Harrington Discovery Institute. The company’s existing investors including Advent Life Sciences and Belinda Termeer also participated and provided initial seed financing instrumental to meeting key milestones.

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Proceeds from the financing will be used to advance the company’s development-stage small molecule drug, an allosteric protein translation modulator targeting eIF4E, into first-in-man, first-in-mechanism clinical studies in advanced metastatic breast cancer. The proceeds will also support expansion of the company’s pipeline of emerging oncology indications.

PIC Therapeutics is targeting a fundamental mechanism at the convergence of many oncogenic signaling pathways that results in apoptotic cancer cell death while sparing normal cells. Allosteric modulation of eIF4E offers many advantages to previous approaches, and simultaneously addresses multiple drivers of pharmacology, allowing the company’s small molecules to truly drive differential CAP dependent translation in target cells.

Preclinical studies show that PIC compounds modulate, but do not block, protein translation. PIC compounds mechanistically modulate cellular proteomes, leading to rapid and significant reduction in cancer cell viability via apoptosis. Inducing apoptosis rather than senescence is an important distinguishing feature of PIC’s approach to this elusive target.

"This financing from a committed and distinguished investor syndicate, which includes new and existing investors, underscores the progress we’ve made to advance our lead program toward our goal of cancer therapies that broadly address cancer-driving oncogenes via a fundamental mechanism in protein translational modulation," said Katherine Bowdish, Chief Executive Officer of PIC Therapeutics. "We are well positioned to build a leading mechanistic-based oncology company that brings promising science to cancer patients with drug resistant tumors."

"We are excited to partner with PIC Therapeutics as they build a differentiated targeted oncology company, and we look forward to supporting the team as they work towards achieving key development goals over the coming years," said Tal Zaks, Partner of OrbiMed Advisors.

"Founded on the scientific work of Dr. Gerhard Wagner at Harvard University and Dr. Nahum Sonenberg at McGill University, PIC Therapeutics has developed a truly novel approach for eIF4E, an important target in resistant cancers. We are pleased to work with the PIC team and its investors to enable new frontiers in targeted mechanistic oncology with the potential to transform the treatment paradigm for cancer patients," commented Gerry Brunk, Managing Director of Lumira Ventures.

On October 19, 2022 Monopar Therapeutics Inc. (Nasdaq: MNPR), a clinical-stage biopharmaceutical company focused on developing proprietary therapeutics designed to extend life or improve the quality of life for cancer patients, reported that the abstract on its drug candidate MNPR-202 has been selected for a poster presentation at the 64th ASH (Free ASH Whitepaper) Annual Meeting & Exposition (ASH 2022) (Press release, Monopar Therapeutics, OCT 19, 2022, View Source [SID1234622182]). ASH (Free ASH Whitepaper) 2022, being held in New Orleans, is the premier event in malignant and non-malignant hematology. This poster will be the first release of data from Monopar’s ongoing collaboration with Dr. Anand Jeyasekharan of the Cancer Science Institute of Singapore, National University of Singapore Hospital.

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Dr. Jeyasekharan is exploring how MNPR-202 affects DNA damage response and immune system pathways in cancer cells, resulting in cell death. The aim is to identify cancer indications where MNPR-202 could have significant potential as a monotherapy and/or in combination with immunotherapy. MNPR-202 was designed to retain the same potentially non-cardiotoxic backbone as Monopar’s clinical-stage doxorubicin analog camsirubicin, but is modified at other positions which may enable it to work in certain cancers that are resistant to camsirubicin and doxorubicin.

"We have been thrilled with the progress of the collaboration," said Chandler Robinson, MD, Monopar’s Chief Executive Officer. "Dr. Jeyasekharan is a leading expert on how the immune system recognizes cancer cells upon DNA-damaging chemotherapy, and his insights and preclinical experiments have yielded promising and helpful data. We are excited for the opportunity to share the findings at ASH (Free ASH Whitepaper) 2022."

On October 19, 2022 Abbott (NYSE: ABT) reported that financial results for the third quarter ended Sept. 30, 2022 (Press release, Abbott, OCT 19, 2022, View Source [SID1234622181]).

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Third-quarter sales of $10.4 billion decreased 4.7 percent on a reported basis and increased 1.3 percent on an organic basis, which excludes the impact of foreign exchange.
GAAP diluted EPS1 was $0.81 in the third quarter. Excluding specified items, adjusted diluted EPS was $1.15.
Abbott is raising its full-year 2022 EPS guidance. Abbott projects full-year diluted EPS on a GAAP basis of $3.75 to $3.81 and projects adjusted diluted EPS of $5.17 to $5.23.
Full-year 2022 guidance assumes COVID-19 testing-related sales of $7.8 billion, which includes sales of $7.3 billion through September 2022 and projected sales of $0.5 billion in the fourth quarter.
U.S. Medical Devices sales grew 11.3 percent in the third quarter, led by strong double-digit growth in Electrophysiology, Structural Heart and Diabetes Care.
In September, Abbott presented new data showing its FreeStyle Libre continuous glucose monitoring system helped reduce acute diabetes-related events, leading to a 67 percent decrease in hospitalizations in people with Type 2 diabetes on once-daily (basal) insulin therapy.2
During the quarter, Abbott launched its latest-generation FreeStyle Libre 3 system in the U.S., which automatically delivers up-to-the-minute glucose readings and unsurpassed 14-day accuracy3 in the world’s smallest and thinnest3 wearable sensor.
During the quarter, following a manufacturing stoppage earlier this year, Abbott restarted production of Similac as well as EleCare and metabolic infant formulas at its Sturgis, Michigan, facility.
"Our results and increased guidance in the current macroeconomic environment reflect the strength of our diversified business model and execution," said Robert B. Ford, chairman and chief executive officer, Abbott. "We’re particularly pleased with improving sales growth rates in U.S. Medical Devices, which is being fueled by several recent product launches, as well as continued strong performance in Established Pharmaceuticals."

THIRD-QUARTER BUSINESS OVERVIEW
Note: Management believes that measuring sales growth rates on an organic basis is an appropriate way for investors to best understand the underlying performance of the business. Organic sales growth excludes the impact of foreign exchange.

* Total Abbott sales include Other Sales of approximately $3 million in 3Q22 and approximately $8 million in 9M22.

n/a = Not Applicable.

Note: In order to compute results excluding the impact of exchange rates, current year U.S. dollar sales are multiplied or divided, as appropriate, by the current year average foreign exchange rates and then those amounts are multiplied or divided, as appropriate, by the prior year average foreign exchange rates.

Total sales in the third quarter were negatively impacted by year-over-year declines in COVID-19 testing-related sales and a manufacturing stoppage initiated in February of certain infant formula products manufactured at Abbott’s Sturgis, Michigan, facility. Excluding COVID-19 testing-related sales4 and the U.S. sales associated with the manufacturing stoppage5 in the current and prior years, total worldwide sales decreased 0.6 percent on a reported basis and increased 6.0 percent on an organic basis in the third quarter.

Worldwide Nutrition sales decreased 14.9 percent on a reported basis and 10.3 percent on an organic basis in the third quarter. Total worldwide Nutrition and Pediatric Nutrition sales were negatively impacted by a manufacturing stoppage initiated in February of certain infant formula products manufactured at Abbott’s Sturgis, Michigan, facility. Abbott resumed production at the facility during the third quarter. International Pediatric sales were negatively impacted by challenging market conditions in China.

In Adult Nutrition, global sales decreased 4.0 percent on a reported basis and increased 2.4 percent on an organic basis, led by Ensure, Abbott’s market-leading complete and balanced nutrition brand.

Diagnostics sales in the third quarter were negatively impacted by year-over-year declines in COVID-19 testing-related sales. Global COVID-19 testing-related sales were $1.7 billion in the third quarter of 2022 compared to $1.9 billion in the third quarter of last year.6 Excluding COVID-19 testing-related sales, worldwide Diagnostics sales declined 0.2 percent on a reported basis and increased 6.1 percent on an organic basis in the third quarter.4

Established Pharmaceuticals sales increased 4.9 percent on a reported basis and 12.2 percent on an organic basis in the third quarter.

Key Emerging Markets include several emerging countries that represent the most attractive long-term growth opportunities for Abbott’s branded generics product portfolio. Sales in these geographies increased 6.2 percent on a reported basis and 13.0 percent on an organic basis, led by strong growth in several geographies including India, China, Brazil and Vietnam and several therapeutic areas, including cardiometabolic, gastroenterology and central nervous system/pain management.

Other sales increased 1.1 percent on a reported basis and 9.9 percent on an organic basis in the quarter.

Worldwide Medical Devices sales decreased 0.5 percent on a reported basis and increased 6.4 percent on an organic basis in the third quarter. Sales growth in the U.S. was led by strong double-digit growth in Electrophysiology, Structural Heart and Diabetes Care. Internationally, sales growth was negatively impacted by intermittent COVID-19 lockdown restrictions in China as well as supply constraints in certain areas, most notably Electrophysiology.

In Diabetes Care, FreeStyle Libre sales were approximately $1.0 billion in the quarter, including U.S. growth of more than 40 percent. International FreeStyle Libre sales were negatively impacted by supply constraints of Abbott’s first-generation FreeStyle Libre system in certain emerging markets.

ABBOTT’S EARNINGS-PER-SHARE GUIDANCE
Abbott is raising its projected full-year 2022 diluted earnings per share under GAAP to $3.75 to $3.81. Abbott forecasts specified items for the full-year 2022 of $1.42 per share primarily related to intangible amortization, costs related to a voluntary recall, asset impairments, expenses associated with acquisitions, restructurings and cost reduction initiatives and other net expenses. Excluding specified items, Abbott is raising its projected adjusted diluted earnings per share to $5.17 to $5.23 for the full-year 2022.

ABBOTT DECLARES 395TH CONSECUTIVE QUARTERLY DIVIDEND
On Sept. 15, 2022, the board of directors of Abbott declared the company’s quarterly dividend of $0.47 per share. Abbott’s cash dividend is payable Nov. 15, 2022, to shareholders of record at the close of business on Oct. 14, 2022.

Abbott has increased its dividend payout for 50 consecutive years and is a member of the S&P 500 Dividend Aristocrats Index, which tracks companies that have annually increased their dividend for at least 25 consecutive years.

On October 19, 2022 VIB, Flanders’ leading life sciences institute, and Surface Oncology (Nasdaq: SURF), a clinical-stage immuno-oncology company developing next-generation immunotherapies that target the tumor microenvironment, reported jointly the publication of a study entitled, "Structural basis of activation and antagonism of receptor signaling mediated by interleukin-27: Cell Reports," in Cell Reports, a leading scientific journal. The study was a collaborative research effort between the Unit for Structural Biology at the VIB-University of Ghent Center for Inflammation Research and Surface Oncology (Press release, Surface Oncology, OCT 19, 2022, View Source [SID1234622180]).

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"In this study, we have shown how the IL-27 heterodimer is formed, and how the cytokine uniquely docks with its receptor to form the IL-27 signaling complex, providing new insights into IL-27 cytokine biology," said Savvas Savvides, Professor and Group Leader at Ghent University and the VIB Center for Inflammation Research. "The elucidation of the structure of IL-27 and its complex with its signaling receptor provides invaluable data to support the ongoing mechanistic interrogation, engineering, and therapeutic targeting of IL-27."

"SRF388 is a fully human anti-IL-27 antibody designed to inhibit the activity of this immunosuppressive cytokine, and this study provides important structural evidence that the antibody directly competes with the IL-27 receptor to prevent downstream signaling of the cytokine," said Vito Palombella, Chief Scientific Officer at Surface Oncology. "IL-27 has been implicated as an immunosuppressive cytokine in several tumor microenvironments and understanding the mechanistic basis of SRF388’s inhibitory activity will help inform its ongoing clinical development."

Summary of key data:

IL-27 is comprised of p28 and EB13 subunits which are uniquely organized into a heterodimeric assembly distinct from other members of the IL-12 family of cytokines.
The elucidated crystal structure of IL-27 and its receptor reveals the presence of at least 4 different sites that are important for the assembly of the signaling complex and which potentially can be used as targeting sites to disrupt IL-27’s structure and subsequently its immunosuppressive function.
Analyses reveal that SRF388 and the IL-27 receptor contend for the same binding epitope on IL-27, with SRF388 competitively inhibiting IL-27 receptor activity, providing structural evidence for SRF388’s potent antagonistic properties.
Details on the study by Katarzyna Składanowska, Yehudi Bloch et al. can be found in the October 18 issue of Cell Reports [VOLUME 41, ISSUE 3, 111490, View Source(22)01340-7. Additional authors include Daniel Aldridge and Christopher Hunter, Ph.D., chair of the Department of Pathobiology at the University of Pennsylvania School of Veterinary Medicine and a member of the Surface Oncology Scientific Advisory Board.

About SRF388
SRF388 is a fully human anti-IL-27 antibody designed to inhibit the activity of this immunosuppressive cytokine. Surface Oncology has identified particular tumor types, including liver, kidney and lung cancer, where IL-27 appears to play an important role in the immunosuppressive tumor microenvironment and may contribute to resistance to treatment with checkpoint inhibitors. SRF388 targets the rate-limiting p28 subunit of IL-27, and preclinical studies have shown that treatment with SRF388 blocks the immunosuppressive biologic effects of IL-27, resulting in immune cell activation in combination with other cancer therapies including anti-PD-1 therapy, as well as potent anti-tumor effects as a monotherapy. Furthermore, Surface Oncology has identified a potential biomarker associated with IL-27 that may be useful in helping to identify patients most likely to respond to SRF388. In November 2020, Surface announced that SRF388 was granted Orphan Drug designation and Fast Track designation for the treatment of refractory hepatocellular carcinoma from the FDA.

On October 19, 2022 Jazz Pharmaceuticals plc (Nasdaq: JAZZ) and Zymeworks Inc. (NYSE: ZYME) reported that Jazz and Zymeworks’ subsidiary, Zymeworks BC Inc., have entered into an exclusive licensing agreement under which Jazz will acquire development and commercialization rights to Zymeworks’ zanidatamab across all indications in the United States, Europe, Japan and all other territories except for those Asia/Pacific territories previously licensed by Zymeworks (Press release, Jazz Pharmaceuticals, OCT 19, 2022, View Source [SID1234622179]).

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"Zanidatamab is a novel HER2-targeted bispecific antibody with biparatopic binding and the potential to transform the current standard of care in multiple HER2 expressing cancers," said Rob Iannone, M.D., M.S.C.E., executive vice president, global head of research and development of Jazz Pharmaceuticals. "This agreement reflects Jazz’s strategic focus on opportunities where we can not only apply advanced technologies to address critical unmet patient needs, but where we can also leverage Jazz’s existing integrated capabilities and global infrastructure to commercialize efficiently. Zanidatamab has the potential to deliver significant long-term value and meaningfully contribute to Vision 2025 as we aim to deliver at least five novel therapies to patients by the end of the decade. We are pleased to expand our growing oncology pipeline with a late-stage program, and today’s announcement further demonstrates our commitment to delivering novel oncology therapies."

"In partnering with Jazz, we are thrilled to be working with a leading global biopharmaceutical team that brings a wealth of development and commercial experience in oncology and shares our vision and passion for working hard every day to improve outcomes for cancer patients around the world," said Kenneth Galbraith, Chair & CEO of Zymeworks. "Zymeworks and Jazz are committed to advancing the development of zanidatamab as rapidly as possible, with the potential to provide a foundational HER2-targeted therapy for patients with difficult-to-treat cancers who currently have limited treatment options."

Zanidatamab, a HER2-targeted bispecific antibody with novel mechanisms of action, has demonstrated compelling anti-tumor activity in several HER2-expressing cancers, both as monotherapy and in combination with chemotherapy and other agents. Zanidatamab is currently in pivotal trials as a second-line treatment for HER2-expressing biliary tract cancer (BTC) and as a first-line treatment for HER2-positive gastroesophageal adenocarcinoma (GEA). In BTC, where no HER2-targeted therapies are currently approved, the U.S. Food and Drug Administration (FDA) has granted Breakthrough Therapy designation for zanidatamab, positioning it as a potential first-in-class therapy. In GEA, based on Phase 2 data, zanidatamab in combination with chemotherapy has the potential to be a best-in-class therapy.

Zanidatamab is based on Zymeworks’ Azymetric platform and can simultaneously bind two non-overlapping epitopes of HER2, which is known as biparatopic binding. This innovative design results in multiple novel mechanisms of action including dual HER2 signal blockade, enhanced binding and removal of HER2 protein from the cell surface, and potent effector function leading to encouraging antitumor activity in patients.

FDA has granted Breakthrough Therapy designation for zanidatamab in patients with previously treated HER2 gene-amplified BTC, and two Fast Track designations for zanidatamab, one as a single agent for refractory BTC and one in combination with standard of care chemotherapy, for first-line GEA. These designations mean zanidatamab is eligible for Accelerated Approval, Priority Review and Rolling Review, as well as FDA guidance on an efficient drug development program. Zanidatamab has also received Orphan Drug designations from FDA for the treatment of biliary tract and gastric cancers, as well as Orphan Drug designation from the European Medicines Agency for the treatment of gastric cancer.

Transaction Terms

Under the terms of the agreement, Jazz will receive an exclusive license to develop and commercialize zanidatamab in the United States, Europe, Japan and all other territories except for those Asia/Pacific territories that Zymeworks previously licensed to BeiGene, Ltd. Zymeworks is eligible to receive a $50 million upfront payment, following receipt of the clearance relating to the United States Hart-Scott Rodino Antitrust Improvements Act of 1976 (such clearance, the "HSR Clearance"), and should Jazz decide to continue the collaboration following readout of the top-line clinical data from HERIZON-BTC-01, a second, one-time payment of $325 million. Zymeworks is also eligible to receive up to $525 million upon the achievement of certain regulatory milestones and up to $862.5 million in potential commercial milestone payments, for total potential payments of up to $1.76 billion. Pending approval, Zymeworks is eligible to receive tiered royalties between 10% and 20% on Jazz’s net sales.

Closing of the agreement is subject to expiration or termination of the waiting period under the Hart-Scott-Rodino Act of 1976. The transaction is expected to close within the 2022 calendar year.

Zymeworks management will host a conference call and webcast for investors and analysts on October 19, 2022, at 8:00 a.m. ET. Interested parties should refer to the separate press release issued by Zymeworks for additional details.

About Zanidatamab

Zanidatamab is a bispecific antibody, based on Zymeworks’ Azymetric platform, that can simultaneously bind two non-overlapping epitopes of HER2, known as biparatopic binding. This unique design results in multiple mechanisms of action including dual HER2 signal blockade, increased binding and removal of HER2 protein from the cell surface, and potent effector function leading to encouraging antitumor activity in patients. Zymeworks is developing zanidatamab in multiple Phase 1, Phase 2 and pivotal clinical trials globally as a targeted treatment option for patients with solid tumors that express HER2.

About Biliary Tract Cancers

Biliary tract cancers (BTC), including gallbladder cancer and cholangiocarcinoma, account for approximately 3% of all adult cancers and are often associated with a poor prognosis1. Globally, more than 210,000 people are diagnosed with BTC every year2 and most patients (> 65%) are diagnosed with tumors that cannot be removed surgically. The human epidermal growth factor receptor 2 (HER2) is a well-validated target for anti-cancer therapy. About 5% to 19% of patients with BTC have tumors that express HER23 and may be positioned for potential benefit from HER2-targeted therapy. Currently no HER2-targeted therapy has been approved for the treatment of BTC.

About Gastroesophageal Adenocarcinoma

Gastroesophageal adenocarcinoma (GEA) is the fifth most common cancer worldwide and approximately 20% of patients are HER2-positive. HER2-positive GEA has high morbidity and mortality, and patients are urgently in need of new treatment options.