TriSalus Life Sciences and MD Anderson Announce Strategic Research Collaboration to Evaluate Treatment of Solid Tumors

On April 8, 2021 The University of Texas MD Anderson Cancer Center and TriSalus Life Sciences, an emerging immuno-oncology company committed to transforming outcomes for patients with liver and pancreatic tumors, reported a strategic research collaboration to evaluate the treatment of tumors of the pancreas and liver by integrating interventional delivery of SD-101, an investigational toll-like receptor 9 (TLR9) agonist, in combination with checkpoint inhibition immunotherapy (Press release, TriSalus Life Sciences, APR 8, 2021, View Source [SID1234577715]).

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Under the agreement, MD Anderson and TriSalus will collaborate on studies evaluating the administration of investigational SD-101 intravascularly via TriSalus’ Food and Drug Administration (FDA) cleared, proprietary Pressure-Enabled Drug Delivery (PEDD) technology across a range of liver and pancreatic solid tumors. The initial study will focus on liver metastases from uveal melanoma, followed by studies focused on metastatic disease from pancreatic ductal adenocarcinoma and colorectal cancer. Programs for hepatocellular carcinoma and locally advanced pancreatic ductal adenocarcinoma also are under development. TriSalus will provide funding and technology for the studies.

"We’re pleased to collaborate with MD Anderson in pursuit of our collective goal to improve outcomes for patients with tumors of the liver and pancreas. The goal of these studies is to augment the potential of existing therapies through novel drug delivery technology and to investigate the strategic modulation of immune microenvironments with investigational candidate SD-101," said Steven Katz, M.D., Chief Medical Officer, TriSalus Life Sciences. "Collaborations such as this are an integral part of our development strategy to evaluate treatments to help overcome the challenges inherent to solid tumors and enable a broader population of cancer patients to benefit from immunotherapy."

SD-101 has been evaluated in phase 2 studies in advanced cutaneous melanoma and head and neck cancer.1,2 Early data suggests SD-101 augmented responsiveness to checkpoint inhibitors through stimulation of innate immune cells, along with favorable programming of the T cell population.3 The planned studies under the research collaboration are intended to deliver SD-101 deep into the vasculature of solid tumors using PEDD, a technique not previously possible using standard delivery approaches.4

Solid tumors continue to represent one of the single biggest hurdles to successful cancer treatment.5 High levels of pressure inside solid tumors prevent the delivery of oncology therapeutics, with less than 1% of therapy penetrating solid tumors in some circumstances.6,7 TriSalus developed PEDD to deliver immuno-oncology therapeutics directly into the vasculature of solid tumors.

"Tumors in the pancreas and liver are notoriously difficult to treat effectively, and these patients need new therapeutic options. Our collaboration with TriSalus provides a unique opportunity to evaluate immunotherapy in combination with a novel delivery approach," said Sapna Patel, M.D., associate professor of Melanoma Medical Oncology at MD Anderson. "We look forward to our work together to advance new treatments aimed at improving clinical outcomes and the lives of our patients."

ImmunoPrecise Launches TATX-112 Candidate Antibody Program, for the Treatment of Cancer and Alzheimer’s Disease

On April 8, 2021 IMMUNOPRECISE ANTIBODIES LTD. (the "Company" or "IPA") (NASDAQ: IPA) (TSX VENTURE: IPA) a leader in full-service, therapeutic antibody discovery and development, reported that its subsidiary Talem Therapeutics LLC ("Talem") has advanced development of a candidate panel of vetted, novel, therapeutic antibodies, collectively referred to as TATX-112, against an undisclosed target, into formal lead candidate characterization (Press release, ImmunoPrecise Antibodies, APR 8, 2021, View Source [SID1234577731]).

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It is well documented that certain genes, when mutated and expressed in different tissues and organs, may play a role in more than one disease.

Oncology

The target is a protein receptor that is overexpressed in a variety of types of deadly cancers. In solid tumors, stimulation of the target by its ligand is described to result in activation of intracellular signaling pathways that promote cancer cell growth, survival, invasiveness, metastatic behavior, and suppress chemotherapeutic sensitivity of the tumor cells. Therefore, interference with the target signaling is anticipated to be an attractive approach to induce tumor suppression, or halting tumor cell growth. As current therapies focusing on inhibiting intracellular target signaling consist primarily of non-target selective small molecule inhibitors, they may be high risk for unintentionally causing undesirable side-effects to the patient by functionally blocking related receptor proteins, which are more widely expressed in the human body, in parallel. In contrast, Talem has developed the TATX-112 antibodies with the goal of specifically blocking the interaction between the target and its ligand, e.g. functionally interfering with the target’s biology, which is expected to significantly improve specificity of such tumor therapy due to its relatively higher expression levels in tumors compared to normal tissue. That higher specificity is expected to increase the therapeutic window by lowering the potential risk of side effects and positively impacting treatment efficacy. Additionally, the target’s expression profile makes this membrane protein a promising candidate for antibody-drug conjugate-based therapies.

Neurodegenerative Diseases

In addition to its role in oncology, the target plays a vital role in the nervous system by enhancing neuronal development, survival, protection, and function. Alzheimer’s and other neurodegenerative diseases are associated with reduced expression levels of the target and impaired receptor signaling. Stimulating intracellular target signaling using agonistic antibodies is an appealing therapeutic approach to suppress disease progression with an expectedly higher safety profile than less-selective small molecules. Such therapeutic strategy requires blood-brain-barrier passage which can be facilitated by a bi- or multi-specific antibody format, including an antibody fragment that induces transport over the blood-brain-barrier upon binding.

Talem’s Pipeline

As the different clinical application options for TATX-112 antibodies require a functionally diversified set of lead candidates and antibody format flexibility, Talem relied on two of IPA’s proprietary target-enrichment antibody discovery platforms, B cell Select and DeepDisplay. Following selection of both target-reactive B cells from target immunized chicken and human scFvs from IPA’s in-house phage libraries, 50 sequence-unique antibodies of particular interest were prioritized for more in-depth characterization to bin antibodies for further (indication-specific) clinical development.

In addition to TATX-112, Talem is continuing development efforts of its other potential products leveraging its pipeline of highly differentiated therapeutic antibody programs for the potential treatment of various disease areas, including heart disease, inflammation, infectious diseases and cancer. The Company’s most advanced development program, TATX-03 ("anti-SARS PolyTope"), is a fully human, synergistic, antibody cocktail containing potently neutralizing antibodies against non-overlapping epitopes on SARS-CoV-2.

"Generating a diversified anti-target antibody panel during the discovery phase is key to a successful therapeutic lead campaign, in particular for programs that are aimed at obtaining antibodies with different modes of action," stated ImmunoPrecise President and CEO, Dr. Jennifer Bath. Leveraging our robust target-enrichment antibody discovery technologies, B cell Select and DeepDisplay, we discovered a highly sequence diverse pool of anti-target antibodies, which allows proper down-selection of the best-performing lead candidates for further development, thereby increasing the chance of successful clinical application."

About B cell Select

IPA’s B cell Select platform enables the interrogation of a greater diversity of an antibody repertoire. By interrogating isolated B cells, IPA can analyze full organism repertoires with very little manipulation. This proprietary platform is species independent allowing for the generation of antibodies from samples not possible using other methods. B cell Select has the potential to develop antibodies from any species (including humans) as well as from any tissue. As the platform explores the entire antibody repertoire, it provides the opportunity to develop antibodies for anything that is possible in an animal’s immune repertoire including any protein class, complex therapeutic targets, post-translational modifications, and small molecules.

The B cell Select platform enables the interrogation of 10 million blood cells to generate native monoclonal antibodies from immunized animals that specifically target an antigen. The B cell Select process takes place early in the antibody development process allowing for the rapid selection of top candidates, drastically increasing the success rate of antibody discovery. The platform also harnesses the power of the immune system to generate natural pairing of the antibodies produced by selected B cells.

About DeepDisplay

IPA’s DeepDisplay is a phage display approach based on building custom immune libraries from multiple species, including transgenic animals, or the selection of antigen-specific recombinant antibody fragments from our proprietary human or llama phage libraries. Our libraries have been made from human patient and naïve (scFv) repertoires, as well as from naïve llama (VHH) repertoires. Custom immune libraries are prepared from blood, spleen, lymph nodes, and bone marrow of immunized animals or humans and capture the entire immune repertoire for panning, rescue, and identification of unique antibodies with pre-specified characteristics.

Magellan Rx Management and Trapelo Health to Offer Precision Oncology Platform for Next-Generation Care

On April 8, 2021 Magellan Rx Management, a division of Magellan Health, Inc. (NASDAQ: MGLN), and Trapelo Health, reported that they are collaborating to champion a more comprehensive, integrated approach to value-based care in the new era of precision oncology treatments (Press release, Magellan Health Services, APR 8, 2021, View Source [SID1234577747]).

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The collaboration combines the unique strengths of the two organizations: Magellan Rx’s comprehensive oncology management solution, and the Trapelo precision-medicine platform that enables fast, precise test and treatment decision support, including test order management, results interpretation and streamlined prior authorizations.

To learn more, listen to an in-depth conversation with leaders from both companies on the Precision Medicine Podcast.

The role of actionable molecular tests is growing significantly in the selection of advanced cancer therapies. The provision of high-quality cancer care requires the appropriate identification of patients to be tested while ensuring the correct tests are ordered for those patients. Accurate interpretation of the test results, based on current medical evidence is crucial. Clinical data is being published at such an unprecedented pace that providers and payers need access to a shared, unbiased decision-support technology.

The Trapelo decision-support platform ensures comprehensive, personalized testing for every cancer patient every time while allowing payers autonomy regarding contracted lab selection. Using Trapelo, oncologists will be able to order the appropriate molecular tests and receive results faster through a simplified and automated prior authorization process. Treatment selection is also streamlined by identifying relevant treatments based on molecular test results, evidence-based guidelines and clinical trials. Trapelo’s patent-pending technology incorporates health plan policy and eliminates unnecessary medical redocumentation to speed approvals for both cancer genomic testing and drug therapy selection.

"We recognize that contemporary oncology care requires changes in the approach to oncology management," said Caroline Carney, M.D., Chief Medical Officer of Magellan Health and Magellan Rx Management. "This collaboration allows us to extend the value of the services we can provide to our health plan customers, and strengthens our shared commitment to ensuring that every patient receives the opportunity for the best possible outcome."

This solution will support Magellan Rx Management’s medical pharmacy program which offers comprehensive, patient-focused oncology solutions and cost savings so that payers can deliver true value and improved quality of life. Magellan Rx’s offering includes integrated, flexible interventions that address the many facets of cancer care, such as: guideline-supported prior authorization; drug wastage; personalized dosing; oral oncology management; post-service claim edits; provider network management; specialty formulary solutions; site of service; and holistic patient care management.

"We are delighted to be working with Magellan. This gives us a significant opportunity to advance our vision for a more collaborative approach in oncology that streamlines workflow and eases administrative burden for providers, labs and payers while improving patient access and outcomes," added Clynt Taylor, CEO of Trapelo Health.

Ionis prices private placement of convertible senior notes

On April 8, 2021 Ionis Pharmaceuticals, Inc. (NASDAQ: IONS) reported the pricing of $550.0 million aggregate principal amount of 0% Convertible Senior Notes due 2026 (the "notes") in a private placement (the "offering") to qualified institutional buyers pursuant to Rule 144A under the Securities Act of 1933, as amended (the "Securities Act") (Press release, Ionis Pharmaceuticals, APR 8, 2021, View Source [SID1234577764]). The aggregate principal amount of the offering was increased from the previously announced offering size of $500.0 million. Ionis also granted the initial purchasers of the notes an option to purchase, within the 13-day period beginning on, and including, the date on which the notes are first issued, up to an additional $82.5 million aggregate principal amount of notes from Ionis. The sale of the notes is expected to close on April 12, 2021, subject to customary closing conditions.

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The notes will be general unsecured obligations of Ionis, will not bear regular interest and the principal amount of the notes will not accrete. The notes will mature on April 1, 2026, unless earlier converted or repurchased.

Ionis estimates that the net proceeds from the offering will be approximately $536.2 million (or approximately $616.8 million if the initial purchasers exercise their option to purchase additional notes in full), after deducting the initial purchasers’ discounts and commissions and estimated offering expenses payable by Ionis. Ionis expects to use approximately $257.0 million of the net proceeds from the offering to repurchase approximately $247.9 million in aggregate principal amount of its 1% Convertible Senior Notes due 2021 (the "2021 notes") in privately negotiated transactions. In addition, Ionis expects to use approximately $40.8 million of the net proceeds from the offering to pay the cost of the convertible note hedge transactions described below (after such cost is partially offset by the proceeds to Ionis from the sale of the warrant transactions described below). Ionis expects to use the remaining net proceeds from the offering for general corporate purposes, including expansion of manufacturing, research and development, and commercial infrastructure to support its wholly owned pipeline.

Before January 1, 2026, holders will have the right to convert their notes only upon the satisfaction of specified conditions and during certain periods. On or after January 1, 2026 until the close of business on the second scheduled trading day immediately preceding the maturity date, holders may convert all or any portion of their notes at any time. Upon conversion, Ionis will pay or deliver, as the case may be, cash, shares of its common stock or a combination of cash and shares of its common stock, at its election. The conversion rate will initially be 17.2902 shares of Ionis’ common stock per $1,000 principal amount of notes (equivalent to an initial conversion price of approximately $57.84 per share of Ionis’ common stock). The initial conversion price represents a premium of approximately 32.5% over the last reported sale price of $43.65 per share of Ionis’ common stock on April 7, 2021. The conversion rate will be subject to adjustment in some events but will not be adjusted for any accrued or unpaid special interest.

Ionis may not redeem the notes prior to the maturity date, and no sinking fund is provided for the notes.

If Ionis undergoes a "fundamental change" (as defined in the indenture for the notes), then, subject to certain conditions and limited exceptions, holders may require Ionis to repurchase for cash all or any portion of their notes at a fundamental change repurchase price equal to 100% of the principal amount of the notes to be repurchased, plus accrued and unpaid special interest, if any, to, but excluding, the fundamental change repurchase date. In addition, following certain corporate events that occur prior to the maturity date, Ionis will, in certain circumstances, increase the conversion rate for a holder who elects to convert its notes in connection with such a corporate event.

In connection with the pricing of the notes, Ionis entered into convertible note hedge transactions with certain of the initial purchasers or their affiliates and other financial institutions (the "Option Counterparties"). Ionis also entered into warrant transactions with the Option Counterparties. The convertible note hedge transactions are generally expected to reduce potential dilution to Ionis’ common stock upon any conversion of notes and/or offset any cash payments Ionis is required to make in excess of the principal amount of converted notes, as the case may be. However, the warrant transactions would separately have a dilutive effect to the extent that the market price per share of Ionis’ common stock exceeds the strike price of any warrants. The strike price for the warrant transactions will initially be equal to approximately $76.39 per share, which represents a 75.0% premium to the closing sale price of Ionis’ common stock on April 7, 2021. If the initial purchasers exercise their option to purchase additional notes, Ionis expects to enter into additional convertible note hedge transactions and additional warrant transactions relating to the additional notes with the Option Counterparties.

In connection with establishing their initial hedges of the convertible note hedge and warrant transactions, Ionis expects that the Option Counterparties or their respective affiliates will purchase shares of Ionis’ common stock and/or enter into various derivative transactions with respect to Ionis’ common stock concurrently with or shortly after the pricing of the notes. This activity could increase (or reduce the size of any decrease in) the market price of Ionis’ common stock or the notes at that time.

In addition, the Option Counterparties or their respective affiliates may modify their hedge positions by entering into or unwinding various derivatives with respect to Ionis’ common stock and/or by purchasing or selling Ionis’ common stock or other securities of Ionis in secondary market transactions following the pricing of the notes and prior to the maturity of the notes (and are likely to do so during any observation period related to a conversion of notes or in connection with any repurchase of notes by Ionis on any fundamental change repurchase date or otherwise). This activity could also cause or avoid an increase or a decrease in the market price of Ionis’ common stock or the notes, which could affect the ability of noteholders to convert the notes and, to the extent the activity occurs during any observation period related to a conversion of notes, it could affect the amount and value of the consideration that noteholders will receive upon conversion of such notes.

Further, in connection with any repurchases of the 2021 notes, Ionis expects that holders of the 2021 notes who agree to have their 2021 notes repurchased and who have hedged their equity price risk with respect to such notes (the "hedged holders") will unwind all or part of their hedge positions by buying Ionis’ common stock and/or entering into or unwinding various derivative transactions with respect to Ionis’ common stock. The amount of Ionis’ common stock to be purchased by the hedged holders may be substantial in relation to the historic average daily trading volume of Ionis’ common stock. This activity by the hedged holders could increase (or reduce the size of any decrease in) the market price of Ionis’ common stock, including concurrently with the pricing of the notes, resulting in a higher effective conversion price of the notes. Ionis cannot predict the magnitude of such market activity or the overall effect it may have had on the price of the notes in the offering or Ionis’ common stock.

The notes, the warrants and any shares of common stock issuable upon conversion of the notes or exercise of the warrants have not been and will not be registered under the Securities Act, any state securities laws or the securities laws of any other jurisdiction, and unless so registered, may not be offered or sold in the United States absent registration or an applicable exemption from, or in a transaction not subject to, the registration requirements of the Securities Act and other applicable securities laws.

This press release is neither an offer to sell nor a solicitation of an offer to buy any of these securities nor shall there be any sale of these securities in any state or jurisdiction in which such an offer, solicitation or sale would be unlawful prior to the registration or qualification thereof under the securities laws of any such state or jurisdiction.

Exact Sciences schedules first quarter 2021 earnings call

On April 8, 2021 Exact Sciences Corp. (Nasdaq: EXAS) reported that the company plans to release its first quarter 2021 financial results after the close of the U.S. financial markets on May 4, 2021 (Press release, Exact Sciences, APR 8, 2021, View Source [SID1234577716]). Following the release, company management will host a webcast and conference call at 5 p.m. EDT to discuss financial results and business progress.

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First quarter 2021 webcast & conference call details

An archive of the webcast will be available at www.exactsciences.com. A replay of the conference call will be available by calling 800-585-8367 domestically or 416-621-4642 internationally. The access code for the replay of the call is 5789488. The webcast, conference call and replay are open to all interested parties.