Deal Watch: Purdue Continues Move Away From Opioids With Alivio Deal

In its continuing efforts to diversify away from opioid pain drugs, Purdue partners on non-opioid program with Alivio. Rigel licenses Tavalisse rights in all indications go to Spain’s Grifols.

Scrip regularly covers business development and deal-making in the biopharmaceutical industry. Deal Watch is supported by deal intelligence from Strategic Transactions.

Purdue Partners With Alivio On Non-Opioid Bladder-Pain Candidate

Purdue Pharma LP may have built its pain specialty on opioid products, but continues to be under pressure as the opioid epidemic worsens. The firm continued its efforts to move into non-opioid pain drugs with a partnership, announced Jan. 28, with PureTech Health PLC affiliate Alivio Therapeutics to advance a preclinical candidate for interstitial cystitis/bladder pain syndrome (IC/BPS). Developed using Alivio's inflammation-targeting technology, ALV-107 is a non-opioid pain therapy candidate that has relieved pain at all study points post-therapy in preclinical testing.

This is the second partnership Purdue has signed around a non-opioid pain therapy in recent months. In October, it licensed SpineThera Inc.'s preclinical synthetic adrenal corticosteroid SX600, a sustained-release formulation of dexamethasone at undisclosed terms in a deal that also gives Purdue an option to acquire the company. [See Deal] Expected to enter clinical development this year, SX600 will be investigated as a long-lasting (60-90 days) non-opioid analgesic for lower back pain.

Under the current deal, Alivio will get up to $14.75m in upfront cash and near-term license exercise payments under the agreement, and could earn research and development milestones payments of up to $260m along with royalties on product sales. The deal gives Purdue the option to participate in other Alivio investigational compounds and to invest in the biotech's next equity financing.

Spun out of PureTech in 2016, one day after that company also introduced immuno-oncology affiliate Vor Biopharma, Alivio is focused on inflammatory disease and employs technology based on an innovative hydrogel material designed to adhere to and deliver drugs to inflamed tissue based on the degree of inflammation. (Also see "IP Commercializer PureTech Enters CAR-T With Vor BioPharma Start-Up" - Scrip, 12 May, 2016.) The theory is that more drug is released at the site having greater inflammation while healthy tissue is unaffected.

In 2016, as the opioid-addiction crisis garnered more headlines, Purdue moved into psoriasis in a collaboration with Exicure Inc., while also partnering on non-opioid, non-NSAID chronic pain therapies with AnaBios Corp. (Also see "Purdue Signs Two Deals To Diversify Portfolio" - Scrip, 13 Dec, 2016.) In 2017, CEO Mark Timney signaled that Purdue was open for further deal-making in both core therapeutic areas and adjacencies in what he called "a real diversification away from pain." (Also see "Purdue Is Open For Business Deals And Shopping On Multiple Fronts" - Scrip, 1 Feb, 2017.)

The company continues to struggle with the US FDA over whether abuse-deterrent formulations of oxycodone actually are effective in warding off abusive usage. (Also see "Where Is OxyContin Abuse Deterrent Data? Purdue Has Sent Two Studies, But Wait Continues" - Pink Sheet, 27 Jan, 2019.) 

Grifols Gets EU, Turkish Rights To Rigel’s Fostamatinib

After roughly a decade of development, Rigel Pharmaceuticals Inc. finally obtained regulatory approval for SYK inhibitor fostamatinib in the US last April, getting approved as Tavalisse for chronic immune thrombocytopenia (ITP). Now, Rigel has found another way to monetize its drug, licensing European and Turkish rights in all indications to Spain’s Grifols SA.

The license-and-supply agreement announced Jan. 23 brings Rigel $30m up front. The South San Francisco, Calif.-based Rigel can also earn up to $297.5m in regulatory and commercial milestones. Fostamatinib is under regulatory review at the European Medicines Agency for chronic ITP with a decision by the EMA’s Committee on Medicinal Products for Human Use expected by the fourth quarter.

Rigel said fostamatinib could obtain EU approval by the end of 2019, which would trigger a $20m milestone payment. It can also earn stepped double-digit sales royalties on the drug, as high as 30%, in indications including autoimmune hemolytic anemia (AIHA) and IgA nephropathy (IgAN), in Europe and Turkey.

Grifols gets an exit provision under the agreement, allowing it to terminate the deal in 2021, after the pact’s second anniversary, if fostamatinib has not yet gotten EU approval for chronic ITP. For a six-month period, the Spanish firm could elect to return all its rights to the drug to Rigel in exchange for $25m. In October, Rigel licensed rights to Tavalisse in Japan, China, Taiwan and South Korea to Kissei Pharmaceutical Co. Ltd. for $33m up front, plus up to $147m in development and commercial milestones. [See Deal]

Rigel CEO Raul Rodriquez pointed to Grifols’ broad European commercial presence and its established position in the hematology market as drivers behind the deal, and said he hopes the deal can begin generating income for Rigel in 2020. Rigel got US approval of Tavalisse on April 17. (Also see "Rigel Readies Tavalisse For Late-May Launch After FDA Approval" - Scrip, 18 Apr, 2018.) In November, it reported net sales of $4.9m for the product during the third quarter.

Shionogi Expands PeptiDream Discovery Collaboration To BBB-Penetrating Drugs

Japanese bioventure PeptiDream Inc. said on Jan. 23 it had entered into a multi-program collaborative research agreement with Osaka-based Shionogi & Co. Ltd. for the discovery and development of a series of blood brain barrier (BBB)-penetrating peptide-drug conjugates (PDCs).

PeptiDream will use its proprietary Peptide Discovery Platform System (PDPS) technology to identify macrocyclic/constrained peptides against multiple targets selected by Shionogi that are known to be involved in shuttling compounds across the BBB. The peptides will then be optimized to maximize BBB penetration, cargo conjugation and the types of cargoes they are capable of shuttling across the BBB, one of the main physical obstacles in central nervous system drug development.

The companies will then work together to produce novel PDC therapeutics for CNS indications, by combining BBB carrier peptides, identified by PeptiDream, with Shionogi’s own CNS drugs and/or drug candidate compounds.

Detailed financial terms were not disclosed, but PeptiDream will receive an undisclosed upfront payment plus annual R&D funding from Shionogi, and is eligible for payments associated with certain preclinical and clinical development milestones, in addition to royalties on sales of any products containing the PDCs commercialized by Shionogi.

The two partners already have a collaborative agreement dating from February 2016, to develop macrocyclic/constrained peptides against multiple targets of interest selected by Shionogi and to optimize hit peptides into therapeutic peptides or small molecule products, using PeptiDream’s PDPS technology.

Merck KGAA Licenses Vertex Non-Cancer Rights To Two Compounds

Building on a deal signed by the companies two years ago, Merck KGAA has licensed gene-editing rights in six specific genetic disease indications for a pair of compounds to Vertex Pharmaceuticals Inc. Announced Jan. 24, the agreement covers two DNA-dependent protein kinase (DNA-PK) inhibitors: M9831 (formerly known as VX-984) and an additional preclinical compound that went to the German pharma in 2017 for $230m up front. 201720026

Specific financial terms for the new agreement were not disclosed but Merck retains oncology rights to the two compounds. Vertex also gets an option to add indications to the license. Both compounds are part of Merck’s DNA damage response (DDR) inhibitor program.

Merck Healthcare CEO Belen Garijo said his company is rapidly advancing its DDR portfolio in cancer, but is eager to see what Vertex can find out about the molecules’ potential in genetic disease by employing enhancements offered by CRISPR/Cas9-mediated gene editing.

Allergan Signs Up Kowa To Co-Promote Bystolic In US

Kowa Pharmaceuticals America Inc. agreed Jan. 28 to co-promote Allergan PLC's beta blocker Bystolic (nebivolol) in the US, alongside the Japanese pharma's statin product Livalo (pitavastatin). No financial terms were disclosed for what is described as a non-exclusive co-promotion arrangement.

The pact stipulates that Kowa will deploy its roughly 300 cardiometabolic sales reps to promote Bystolic alongside Livalo starting in February to cardiologists and select primary health care provides. Allergan will continue to detail Bystolic in the US to primary health care doctors, as well.

Alnylam Inks Onpattro Commercialization Deal In Israel

RNA-interference specialist Alnylam Pharmaceuticals Inc. signed a deal Jan. 23 with Medison Pharma Ltd. in which the latter will commercialize Onpattro (patisiran), the first commercialized RNAi therapeutic, in Israel, as well as other investigational therapeutics under development in the Alnylam RNAi portfolio.

The agreement between Alnylam and Medison includes Onpattro, approved in the EU in August 2018 for the treatment of hATTR amyloidosis in adults with stage 1 or stage 2 polyneuropathy; givosiran, a late-stage investigational RNAi therapeutic for the treatment of acute hepatic porphyria (AHP); and lumasiran, a late-stage investigational RNAi therapeutic for the treatment of primary hyperoxaluria type 1 (PH1). These medicines are not currently approved for use in Israel; givosiran and lumasiran have not yet been approved by any regulatory authority.

Origenis And Expansion Partner In RNA-Mediated Disease

Germany’s Origenis GMBH announced today it has entered into a global license and collaboration agreement with Expansion Therapeutics Inc. unveiled a global license and collaboration deal Jan. 24 to discover potential small molecule therapies to treat RNA-mediated diseases.

The collaboration will begin with a lead-optimization effort combining Origenis’ MolMind and MoreSystem artificial intelligence discovery platforms to identify candidates for Expansion’s R&D pipeline. Origenis said the partnership joins its capabilities in compound design, chemical synthesis and screening with Expansion’s expertise in discovering and advancing small molecules that interact with RNA.

Origenis’ process is designed to ensure the drug candidates are novel by using Cippix, a tool it claims can create value from “hidden chemical and biological information embedded in patents.” Its discovery process also employs interactive AI feedback to make sure discovered compounds have unique chemical properties and are tested for biological activity, toxicity and stability, the biotech said.

No specific deal terms were disclosed, but San Diego-based Expansion obtains rights to develop products against defined molecular targets, while Origenis earns research funding and could realize development milestone payments.

Circassia Bolts On Another Product In Search To Become Respiratory Business

Oxford, UK-based Circassia Pharmaceuticals PLC announced Jan. 24 that it has bought the rights to commercialize AirNOvent in the US and China from [AIT Therapeutics Inc.] for $7.4m up front with a series of milestone payments to follow.

The rights cover all potential indications in the hospital setting, which includes hypoxic respiratory failure associated with persistent pulmonary hypertension of the newborn (PPHN). AIT anticipates applying to the US FDA for premarket approval (PMA) for AirNOvent in the second quarter for use in the treatment of PPHN. The company also hopes to launch the product in the first half of 2020. Subsequently, AIT plans to seek a label extension for the product’s use in a related indication.

AirNOvent is a portable system that utilizes an electric voltage to produce precise quantities of nitric oxide from the nitrogen and oxygen in air. Steve Harris, Circassia’s CEO, said that buying the US and Chinese commercialization rights to AirNOvent represented “an important milestone” in the firm’s transformation into a commercially focused respiratory pharmaceutical business.

This deal is the latest in a series of moves by the company to establish itself as a respiratory business, the most significant of which was the 2017 acquisition of rights to US commercialization of AstraZeneca PLC’s COPD therapies Tudorza (aclidinium) and Duaklir (aclidinium/formoterol) for $230m. (Also see "Circassia Builds US Respiratory Presence with AstraZeneca Deal" - Scrip, 17 Mar, 2017.)

BioNTech Expands Mab Know-How With Tech Buy

German biotech BioNTech AG will acquire [MAB Discovery GMBH]’s operational antibody generation unit, for an undisclosed sum, it announced Jan. 24.

BioNTech will acquire all assets, employees and proprietary know-how for monoclonal antibody generation from German peer MAB Discovery, which will retain ownership of and all rights to both its proprietary preclinical development pipeline and its existing third-party service agreements.

The acquisition follows a successful collaboration between the companies that started over five years ago, in which antibodies have been generated with MAB Discovery’s proprietary technology that are currently being further developed by BioNTech.

In a statement, BioNTech CEO Ugur Sahin the MAB Discovery technologies “will be utilized with our existing proprietary platforms including RiboMABS, a platform for generating a novel class of mRNA-encoded antibody drug candidates.” The acquisition will be completed and the antibody-generation unit transitioned at the end of the first quarter of 2019.

Elasmogen Licenses NDure Half-Life Extension Technology To ImmunoForge

Elasmogen Ltd., developer of next-generation soloMER biologics, said on Jan. 16 that ImmunoForge has agreed to license Elasmogen’s proprietary NDure half-life extension technology for use in two undisclosed targets.

ImmunoForge will be responsible for all preclinical and clinical development as well as for manufacturing and commercialization of the resulting products. Elasmogen will receive an initial upfront payment in addition to future milestone and royalty payments.

Elasmogen’s NDure albumin binder is based on the company’s soloMER platform. It claims that at just 11 kDa, soloMERs are the smallest naturally occurring binding domains and offer a simple molecular architecture that facilitates easy combination with a wide range of proteins and peptides to enable rapid development of multi-functional therapeutics.

“This licensing agreement provides further validation of the benefits of our soloMER platform and NDure technology,” said Caroline Barelle, CEO of Elasmogen. “At less than 1/10th the size of an antibody, NDure allows rapid re-formatting and simple manufacturing while retaining all of the benefits of high specificity albumin binding.”

Stay tuned for the next issue of Deal Watch. You can read more about other deals that have been covered in depth by Scrip in recent days below:

(Also see "Real Estate Sale, Including Osaka HQ, To Raise $347m For Takeda" - Scrip, 28 Jan, 2019.)	As part of efforts to raise cash to pay for its acquisition of Shire PLC, Takeda Pharmaceutical Co. Ltd. will sell off selected real estate holdings in Japan, including its Osaka HQ, to a mystery buyer.
(Also see "Why Roche Oncology Bet Big On Neoantigen-Directed T-Cell Therapy" - Scrip, 23 Jan, 2019.)	In an interview at J.P. Morgan, Roche's James Sabry explained why it wants to lead the pack in personalized, neoantigen-directed cellular therapy, after announcing tie-up with Adaptive Biotechnologies Corp.
(Also see "Hanmi To Step Up Global Drug Development As Lilly Returns BTK Rights" - Scrip, 23 Jan, 2019.)	Following Eli Lilly & Co.’s decision to return rights to a BTK inhibitor it had licensed in from Hanmi Pharmaceutical Co. Ltd., the South Korean pharma considers independently developing the molecule for other indications and vows to speed up development of other global drug programs.
(Also see "Full Steam Ahead At Ferring To Unlock Microbiome Potential For Reproduction" - Scrip, 22 Jan, 2019.)	Ferring Pharmaceuticals AS is expanding its alliance with the Karolinska Institute to conduct 10 studies designed to improve understanding of the microbiome’s impact on reproductive and gut health challenges.