Almac Discovered Molecule Progresses into Clinical Development with its strategic licensee Vaderis Therapeutics AG

On August 24, 2022 Almac Discovery, a research driven biotech company and member of the Almac Group, reported that is delighted that its novel AKT kinase inhibitor (known as VAD044) is being advanced into a proof-of-concept Phase 1b clinical study for patients suffering from Hereditary Haemorrhagic Telangiectasia (HHT) (Press release, Almac, AUG 24, 2022, View Source [SID1234618588]).

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This patent-protected, allosteric subtype selective AKT kinase inhibitor, which was discovered and taken into early pre-clinical development by Almac Discovery, was out-licensed for all uses, worldwide, to Vaderis Therapeutics AG in May 2020.

After Vaderis’s successful Phase 1a, VAD044 will now be studied by Vaderis Therapeutics AG in their INSIGHT proof-of-concept trial, which aims to provide a thorough understanding of the safety of a once daily, orally administered, AKT inhibitor medication in HHT patients. A total of 80 HHT patients across North America and Europe will be randomised in a double-blind, controlled trial comparing two doses of the medication to placebo. Initiation of the INSIGHT trial follows Health Authority approvals including FDA, Health Canada and key European agencies.

Professor Tim Harrison, Vice President Drug Discovery, commented: "This excellent news from our out-licensing partner, Vaderis Therapeutics AG, represents a further example of Almac Discovery’s mission to discover new, innovative drug candidates for development through external partnerships and collaboration. We look forward, with great anticipation, to monitoring the findings of the INSIGHT trial and wish Vaderis every success as they emerge from stealth mode and progress through the next phase of clinical development for the benefit of HHT patients across the globe."

About Almac Discovery

Almac Discovery is a research driven biotech company dedicated to the discovery and development of First in Class therapeutics across a range of therapeutic areas including neuroscience, muscle-wasting, oncology and inflammation. Almac Discovery focuses on the discovery to preclinical stage, seeking to licence programmes and/or collaborate with a pharmaceutical partner for further development and commercialisation.

Medtronic Reports First Quarter Fiscal 2022 Financial Results

On August 24, 2022 Medtronic plc (NYSE:MDT) reported financial results for its first quarter of fiscal year 2022, which ended July 30, 2021 (Press release, Medtronic, AUG 24, 2022, View Source [SID1234618565]).

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Key Highlights

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Revenue of $8.0 Billion Increased 23% Reported and 19% Organic
GAAP Diluted EPS of $0.56; Non-GAAP Diluted EPS of $1.41
Company Reiterates FY22 Revenue Guidance; Raises Lower End of FY22 EPS Guidance by 5 cents

"FY22 is off to a strong start – Q1 reflects solid execution & continued procedure recovery"
Chairman & CEO Geoff Martha

The company reported first quarter worldwide revenue of $7.987 billion, an increase of 23% as reported and 19% on an organic basis, which excludes the $245 million benefit of foreign currency translation. Revenue growth rates have not been adjusted for the negative impact of the extra selling week in the first quarter of last fiscal year. The company’s first quarter results reflect a strong recovery from the impact of the COVID-19 pandemic on elective procedures that the company experienced in 2020. Unless otherwise stated, all revenue growth rates in this press release are stated on an organic basis, which excludes the impact of foreign currency translation.

As reported, first quarter GAAP net income and diluted earnings per share (EPS) were $763 million and $0.56, respectively, increases of 57% and 56%, respectively. As detailed in the financial schedules included at the end of this release, first quarter non-GAAP net income and non-GAAP diluted EPS were $1.908 billion and $1.41, respectively, increases of 128% and 127%, respectively.

First quarter U.S. revenue of $4.101 billion represented 51% of company revenue and increased 22%. Non-U.S. developed market revenue of $2.601 billion represented 33% of company revenue and increased 20% as reported and 11% organic. Emerging Markets revenue of $1.286 billion represented 16% of company revenue and increased 31% as reported and 25% organic.

"Fiscal 2022 is off to a strong start with our first quarter results coming in ahead of our expectations, reflecting solid execution and continued procedure volume recovery, with most of our businesses at or above pre-COVID levels," said Geoff Martha, Medtronic chairman and chief executive officer. "In addition, we drove market share gains across a number of our businesses, including three of our largest: Cardiac Rhythm Management, Surgical Innovations, and Cranial & Spinal Technologies. Looking ahead, we have some big opportunities in front of us, with near-term milestones in both our renal denervation and surgical robotics businesses. These opportunities, combined with the broader investments we’re making in our pipeline, set us up well to accelerate our top line growth."

Cardiovascular Portfolio
The Cardiovascular Portfolio includes the Cardiac Rhythm & Heart Failure (CRHF), Structural Heart & Aortic (SHA), and Coronary & Peripheral Vascular (CPV) divisions. Cardiovascular first quarter revenue of $2.890 billion increased 19% as reported and 15% organic, driven by low-twenties organic growth in SHA, mid-teens organic growth in CRHF, and high-single digit growth in CPV.

Cardiac Rhythm & Heart Failure first quarter revenue of $1.483 billion increased 19% as reported and 15% organic. Adjusting for the discontinuation of HVAD System sales, CRHF revenue increased 19% organic. Cardiac Rhythm Management revenue increased in the high-teens, driven by low-double digit growth in Defibrillation Solutions and low-twenties growth in Cardiac Pacing Therapies, including low-thirties growth in Leadless Pacemakers on the continued global adoption of the Micra transcatheter pacing system. Cardiac Ablation Solutions revenue increased in the low-thirties on strong adoption of Arctic Front Advance cryoballoon catheters and consoles. Cardiovascular Diagnostics revenue grew in the low-double digits.
Structural Heart & Aortic first quarter revenue of $787 million increased 26% as reported and 21% organic. Structural Heart grew in the high-thirties, driven by mid-thirties growth in transcatheter aortic valves (TAVR), including high-forties TAVR growth in the United States. Cardiac Surgery increased in the high-teens. Aortic declined in the low-single digits, as the financial impact of the previously announced global recall of the Valiant Navion thoracic stent graft system offset low-twenties growth in abdominal aortic aneurysm (AAA) stent grafts.
Coronary & Peripheral Vascular first quarter revenue of $620 million increased 11% as reported and 7% organic. Coronary & Renal Denervation (CRDN) declined in the low-single digits, given the impact of previously announced coronary tenders in China. Excluding China, CRDN revenue grew in the high-single digits. Peripheral Vascular Health increased in the low-twenties, with mid-teens growth in IN.PACT drug-coated balloons and mid-fifties endoVenous growth on strong sales of VenaSeal and ClosureFast superficial vein products and Abre venous stents.
Medical Surgical Portfolio
The Medical Surgical Portfolio includes the Surgical Innovations (SI) and the Respiratory, Gastrointestinal & Renal (RGR) divisions. Medical Surgical first quarter revenue of $2.322 billion increased 29% as reported and 25% organic, with high-thirties organic growth in SI and mid-single digit organic growth in RGR.

Surgical Innovations first quarter revenue of $1.554 billion increased 44% as reported and 39% organic. The division had low-forties growth in Vessel Sealing and high-thirties growth in Advanced Stapling, driven by the continued adoption of the company’s LigaSure, Sonicision, and Tri-Staple technologies. Hernia & Wound Management increased in the mid-thirties, with strength in sutures and hernia product lines.
Respiratory, Gastrointestinal & Renal first quarter revenue of $768 million increased 7% as reported and 3% organic. Patient Monitoring increased in the mid-twenties, with mid-thirties growth in the company’s Nellcor pulse oximetry products. Respiratory Interventions decreased in the mid-twenties, with sales of ventilators declining in the low-forties as demand returns to pre-pandemic levels. Gastrointestinal revenue increased in the high-twenties on low-fifties growth in Esophageal & Gastric. Renal Care Solutions increased in the mid-single digits with strong growth in acute therapies.
Neuroscience Portfolio
The Neuroscience Portfolio includes the Cranial & Spinal Technologies (CST), Specialty Therapies, and Neuromodulation divisions. Neuroscience first quarter revenue of $2.204 billion increased 29% as reported and 26% organic, with high-thirties growth in Neuromodulation and Specialty Therapies and high-teens growth in CST, all on an organic basis.

Cranial & Spinal Technologies first quarter revenue of $1.123 billion increased 19% as reported and 17% organic. Spine & Biologics grew in the low-double digits and Neurosurgery increased in the low-twenties, as spine surgeons continue to adopt the Medtronic ecosystem of spine implants and enabling technology, including Mazor robotics, StealthStation navigation, O-arm imaging, and Midas Rex powered surgical instruments.
Specialty Therapies first quarter revenue of $641 million increased 42% as reported and 37% organic. Neurovascular increased in the high-single digits and ENT increased in the mid-thirties. Pelvic Health increased 134%, driven by continued strong adoption of the InterStim Micro sacral neuromodulation system.
Neuromodulation first quarter revenue of $440 million increased 40% as reported and 37% organic. Brain Modulation increased in the high-thirties, driven by the launch of the Percept PC deep brain stimulation system. Pain Therapies increased in the low-forties, with Targeted Drug Delivery revenue more than doubling on the backlog recovery of replacement procedures, and Pain Stim revenue growing in the mid-twenties on strong uptake of Intellis with DTM SCS therapy. Interventional grew in the low-twenties.
Diabetes
Diabetes first quarter revenue of $572 million increased 2% as reported and declined 3% organic. Diabetes quarterly revenue performance was driven by high-single digit growth in durable pumps, including strong growth in international markets on the continued launch of the MiniMed 780G system. This was offset by mid-teens declines in U.S. sales of consumables and continuous glucose monitoring (CGM) products.

Guidance
The company today reiterated its revenue growth guidance and raised the lower end of its EPS guidance range for fiscal year 2022.

The company continues to expect revenue growth in its fiscal year 2022 to approximate 9% on an organic basis. If current exchange rates hold, revenue growth in fiscal year 2022 would be positively affected by approximately $100 to $200 million.

The company increased its fiscal year 2022 diluted non-GAAP EPS guidance from the prior range of $5.60 to $5.75 to the new range of $5.65 to $5.75, including an estimated 5 to 10 cent positive impact from foreign currency exchange versus a 10 to 15 cent positive impact previously.

"We’re reiterating our revenue guidance for the year while increasing the lower end of our EPS range on the back of our first quarter results," said Karen Parkhill, Medtronic chief financial officer. "We remain focused on accelerating our long-term revenue growth and generating strong returns for our shareholders. In addition to growing our dividend, we are increasing our investments at the front end of major product launches, growing our R&D spend broadly across the company, and executing disciplined tuck-in acquisitions."

Webcast Information
Medtronic will host a webcast today, August 24, at 8:00 a.m. EDT (7:00 a.m. CDT) to provide information about its businesses for the public, investors, analysts, and news media. This webcast can be accessed by clicking on the Investor Events link at investorrelations.medtronic.com(opens new window) and this earnings release will be archived at news.medtronic.com(opens new window). Medtronic will be live tweeting during the webcast on its Newsroom Twitter account, @Medtronic. Within 24 hours of the webcast, a replay of the webcast and transcript of the company’s prepared remarks will be available by clicking on the Investor Events link at investorrelations.medtronic.com(opens new window).

Medtronic plans to report its fiscal year 2022 second, third, and fourth quarter results on November 23, 2021, February 22, 2022, and May 26, 2022, respectively. Confirmation and additional details will be provided closer to the specific event.

April Bio signs license and joint R&D contract with Yuhan

On August , 2022 April Bio reported that the company had signed a technology license and joint research and development contract with Yuhan Corp. to develop a new drug candidate (Press release, AprilBio, AUG 23, 2022, View Source [SID1234643379]).

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Under the accord, the two companies will conduct joint research to develop a new treatment candidate for a dual- and long-acting fusion protein substance applicable to intractable solid cancer based on April Bio’s serum albumin fragment associated (SAFA) platform technology and Yuhan’s new drug R&D capabilities.

April Bio will receive contracted technology fees from Yuhan when they achieve certain milestones, including a down payment. In addition, if approved, April Bio can also receive its share of annual net sales as a recurring technology fee.

If Yuhan enters into a license agreement with a third party, a certain percentage of the proceeds may also be distributed.

However, the two companies did not disclose the investment amount, citing contractual reasons.

"By combining our SAFA platform and dual-action anticancer drug development technology with Yuhan’s immunotherapy development know-how, we plan to develop a substance that can safely and effectively remove cancer cells," April Bio CEO Cha Sang-hoon said. "Our company will focus on research to provide new treatment options to patients suffering from various intractable solid cancers."

Yuhan CEO Cho Wook-je said, "Through this joint research, we anticipate a synergistic effect of the technologies of the two companies and will derive innovative drug candidates from diseases that have unmet needs."

Cho added that the company would continue to promote active open innovation for new drug development.

April Bio entered the KOSDAQ stock market in July after passing the preliminary examination in May. Yuhan participated in April Bio as a strategic investor (SI) to hold a 10.25 percent stake, making it the second largest shareholder.

Erasca and MD Anderson Announce Strategic Research and Development Collaboration in RAS/MAPK-Driven Cancers

On August 23, 2022 Erasca, Inc. (Nasdaq: ERAS), a clinical-stage precision oncology company singularly focused on discovering, developing, and commercializing therapies for patients with RAS/MAPK pathway-driven cancers, and The University of Texas MD Anderson Cancer Center (MD Anderson), reported a strategic research and development collaboration to evaluate multiple agents from Erasca’s pipeline targeting the RAS/MAPK pathway as either single-agent or combination therapies (Press release, Erasca, AUG 23, 2022, View Source [SID1234639376]).

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The initial focus of the alliance will be Erasca’s potentially best-in-class ERK1/2 inhibitor ERAS-007 and its potentially best-in-class SHP2 inhibitor ERAS-601, which together comprise Erasca’s first MAPKlamp combination. ERAS-007 is being investigated in multiple ongoing trials, including in non-small cell lung cancer (NSCLC) as part of the HERKULES-2 master protocol and in gastrointestinal (GI) malignancies as part of the HERKULES-3 master protocol. ERAS-601 is being investigated in multiple ongoing trials, including the FLAGSHP-1 trial in triple wildtype (KRAS/NRAS/BRAF wildtype) colorectal cancer (CRC) and human papillomavirus (HPV)-negative advanced head and neck squamous cell carcinoma (HNSCC) and the HERKULES-2 NSCLC master protocol.

"Our strategic collaboration with MD Anderson broadens the evaluation of ERAS-007 and ERAS-601 and explores additional therapeutic opportunities across our pipeline," said Jonathan E. Lim, M.D., Erasca’s chairman, CEO, and co-founder. "The RAS/MAPK pathway is one of cancer’s most frequently altered pathways, affecting more than 5 million new patients with cancer annually worldwide. We have designed our pipeline to comprehensively shut down this highly oncogenic pathway at multiple critical nodes, and we’re excited to work with MD Anderson to potentially address major unmet needs in the treatment of cancer."

The alliance will build on Erasca’s existing collaborations with MD Anderson investigators Scott Kopetz, M.D., Ph.D., professor of Gastrointestinal Medical Oncology, and David S. Hong, M.D., professor of Investigational Cancer Therapeutics. Kopetz is an investigator in HERKULES-3, which is evaluating ERAS-007 plus encorafenib and cetuximab in BRAF V600E-mutant metastatic CRC and ERAS-007 plus palbociclib in KRAS-mutant/NRAS-mutant CRC and KRAS-mutant pancreatic cancer. Hong is an investigator in FLAGSHP-1, which is evaluating ERAS-601 as monotherapy and in combination with cetuximab in triple wildtype CRC and HPV-negative advanced HNSCC.

"Durability and treatment resistance continue to present challenges in the treatment of lung cancers and GI malignancies, particularly stemming from reactivation of the RAS/MAPK pathway. Erasca’s pipeline of agents that target key nodes, including previously undruggable genetic drivers, has the potential to improve durability and minimize resistance," Kopetz said. "We look forward to collaborating with Erasca to further maximize the potential of promising treatment combinations across its pipeline."

The new strategic collaboration will enhance Erasca’s and MD Anderson’s evaluation of ERAS-007 and ERAS-601 in combination with investigational and standard-of-care agents, including with Erasca’s proprietary pipeline programs, such as the KRAS G12D inhibitor ERAS-4. Under the terms of the five-year agreement, collaborative preclinical and clinical studies will be conducted in NSCLC, GI malignancies and additional mutually agreed-upon indications.

About ERAS-007
ERAS-007 is a potential best-in-class oral ERK1/2 inhibitor being investigated alone or in combination with different inhibitors targeting upstream nodes of the MAPK pathway as part of Erasca’s MAPKlamp strategy. The extracellular signal-regulated kinases (ERK), ERK1 and ERK2, belong to a family of serine-threonine kinases that regulate cellular signaling and comprise the terminal node of the RAS/MAPK pathway. The broad therapeutic potential of ERAS-007 is being investigated initially across a series of HERKULES clinical trials that span multiple tumor types and include both monotherapy and combinations with approved and investigational agents, such as RTK, SHP2, RAS, RAF, and/or cell cycle inhibitors. HERKULES-1 is a Phase 1b/2 clinical trial for ERAS-007 as a single agent and in combination with the SHP2 inhibitor ERAS-601 (together, Erasca’s first MAPKlamp combination) in advanced solid tumors. HERKULES-2 is a Phase 1b/2 clinical trial for ERAS-007 in combination with various agents in patients with NSCLC. HERKULES-3 is a Phase 1b/2 clinical trial for ERAS-007 in combination with various agents in patients with GI cancers.

About ERAS-601
ERAS-601 is a potential best-in-class oral, selective SHP2 inhibitor being investigated alone or in combination. SHP2 acts as a convergent node for receptor tyrosine kinase (RTK) signaling, relaying growth and survival signals from RTKs to intracellular signaling pathways. ERAS-601 is being investigated across a series of clinical trials that span multiple tumor types and include both monotherapy and combinations with approved and investigational agents. FLAGSHP-1 is a Phase 1/1b dose escalation trial evaluating ERAS-601 as a monotherapy in advanced solid tumors and in combination in triple wildtype CRC and HPV-negative advanced HNSCC. HERKULES-2 is a Phase 1b/2 master protocol clinical trial that includes evaluation of ERAS-601 in combination with various agents in patients with NSCLC.

A-Alpha Bio Announces Collaboration with Bristol Myers Squibb to Discover Molecular Glue Targets for Protein Degradation

On August 23, 2022 A-Alpha Bio (A-Alpha), a synthetic biology and machine learning company that measures and engineers protein-protein interactions reported a collaboration with Bristol Myers Squibb to discover molecular glue targets for protein degradation (Press release, A-Alpha Bio, AUG 23, 2022, View Source [SID1234636943]). A-Alpha will identify and characterize novel pairs of E3 ubiquitin ligases and targets that Bristol Myers Squibb will utilize for potential design and development of molecular glues to induce targeted protein degradation.

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The collaboration is the second announced by A-Alpha in the rapidly growing field of targeted protein degradation. Under the agreement, A-Alpha will apply its AlphaSeq and computational platforms to quantitatively measure and analyze protein-protein binding between members of A-Alpha’s proprietary library of E3 ligases. As part of the agreement, A-Alpha Bio will receive upfront and near-term success payments and will be eligible for development milestones and a royalty on product sales.

Targeted protein degradation is an emerging therapeutic modality enabling potential therapeutic intervention otherwise difficult with conventional approaches. A-Alpha’s proprietary platform, AlphaSeq, is uniquely suited to detect weak protein-protein interactions that can be exploited for the discovery of molecular glues.

"We are excited to work with BMS to unlock the next generation of undrugged targets by broadening the search with more E3 ligases and enabling the rational discovery of molecular glues," said David Younger, PhD, Co-Founder and CEO of A-Alpha Bio. "BMS is a pioneer and market leader in targeted protein degradation with marketed products and a strong development pipeline. We are confident that the insights we provide with our AlphaSeq platform and library of E3 ubiquitin ligases will enable BMS to discover high-impact medicines."