Daniela Salvemini. Saint Louis University

MPM backs new biotech in the hunt for non-opi­oid painkiller

A new MPM Cap­i­tal-backed com­pa­ny is join­ing the search for a bet­ter way of treat­ing chron­ic pain.

Six years af­ter its qui­et birth out of a St Louis lab, BioIn­t­er­vene un­veiled  an MPM-led $30 mil­lion Se­ries A fund­ing round to take its lead drug, BIO-205, in­to hu­man proof-of-con­cept stud­ies. They an­nounced a new CSO too: Charles Co­hen, a neu­ro­science vet­er­an of Mer­ck, Bay­er, Ver­tex and most re­cent­ly Xenon.

BIO-205 “demon­strates pro­found ac­tiv­i­ty in mul­ti­ple mod­els of neu­ro­path­ic and in­flam­ma­to­ry pain as both a sin­gle agent and in com­bi­na­tion with mor­phine and gabapentin,” Co­hen said in a state­ment. “If we can re­pro­duce these da­ta in our clin­i­cal tri­als, BIO-205 has the po­ten­tial to ame­lio­rate tremen­dous suf­fer­ing while al­so play­ing a key role in ad­dress­ing the opi­oid epi­dem­ic.”

You can add BioIn­t­er­vene to the grow­ing num­ber of biotechs search­ing for new meth­ods of pain re­lief – a long-dor­mant hunt that’s picked up in the wake of the opi­oid abuse epi­dem­ic. Some of that re­search has fo­cused on re­pur­pos­ing NSAIDs such as ac­eta­minophen. More com­mon­ly, though, re­searchers have looked for new neur­al path­ways.

That in­cludes groups like Xenon, who have fo­cused on in­hibit­ing the NaV1.7 sodi­um re­cep­tor – al­though Roche and Bio­gen both aban­doned their NaV1.7 pro­grams in 2018 amid clin­i­cal fail­ure. Eli Lil­ly-part­nered Cen­trex­ion is us­ing a com­pound found in chili pep­pers that tar­gets the TR­PV1 re­cep­tor. Still, oth­ers have tried to find bet­ter opi­oids based on a con­cept called bi­ased ag­o­nism. Most of the work is ear­ly-stage.

BioIn­t­er­vene comes out of Saint Louis Uni­ver­si­ty pro­fes­sor Daniela Salvem­i­ni’s work on the A3 adeno­sine re­cep­tor (A3AR). The four dif­fer­ent adeno­sine re­cep­tors had long been in­ves­ti­gat­ed for the roles they may play in can­cer, in­flam­ma­tion and im­mune-re­lat­ed dis­eases.

But in 2012 Salvem­i­ni be­gan pub­lish­ing work sug­gest­ing that an A3AR ag­o­nist could “turn off” pain sig­nals from the spinal cord. In 2014, she formed BioIn­t­er­vene to de­vel­op that work in­to treat­ments of chron­ic pain.

The ag­o­nists are the­o­rized to work by restor­ing a form of neu­ro­trans­mis­sion called GA­BA sig­nal­ing that is dis­rupt­ed in cer­tain forms of pain. Over the 6 years lead­ing up to the Se­ries A, Salvem­i­ni pub­lished an­i­mal stud­ies show­ing the ag­o­nist’s po­ten­tial to treat the pain from can­cer drugs and oth­er caus­es.

Neu­ro­path­ic pain has been a par­tic­u­lar­ly thorny area for drug de­vel­op­ers, with the few ex­ist­ing drugs com­ing with sig­nif­i­cant side ef­fects. Salvem­i­ni has in­sist­ed their re­cep­tor can curb pain with­out the side ef­fects.

“The pro­tec­tive ef­fect of A3AR ag­o­nists in sev­er­al mod­els of chron­ic neu­ro­path­ic pain in­clud­ing that caused by wide­ly used chemother­a­peu­tic agents does not de­sen­si­tize over time with con­stant drug ex­po­sure, and there is no risk of ad­dic­tion,” she wrote in a 2015 note in Ex­pert Opin­ion on Ther­a­peu­tic Patents. 

BioIn­t­er­vene will fo­cus first on pain, but they’re ex­plor­ing one oth­er ther­a­peu­tic area: neu­rode­gen­er­a­tion. There are few de­tails yet but Salvem­i­ni pub­lished a patent in No­vem­ber for us­ing A3 ag­o­nists to ame­lio­rate mi­to­chon­dr­i­al in­jury.

That’ll make two ar­eas of high un­met med­ical need for the young biotech – two that have en­snared a long list of biotechs be­fore them.

2019 Trin­i­ty Drug In­dex Eval­u­ates Ac­tu­al Com­mer­cial Per­for­mance of Nov­el Drugs Ap­proved in 2016

Fewer Approvals, but Neurology Rivals Oncology and Sees Major Innovations

This report, the fourth in our Trinity Drug Index series, outlines key themes and emerging trends in the industry as we progress towards a new world of targeted and innovative products. It provides a comprehensive evaluation of the performance of novel drugs approved by the FDA in 2016, scoring each on its commercial performance, therapeutic value, and R&D investment (Table 1: Drug ranking – Ratings on a 1-5 scale).

UP­DAT­ED: FDA’s golodirsen CRL: Sarep­ta’s Duchenne drugs are dan­ger­ous to pa­tients, of­fer­ing on­ly a small ben­e­fit. And where's that con­fir­ma­to­ry tri­al?

Back last summer, Sarepta CEO Doug Ingram told Duchenne MD families and investors that the FDA’s shock rejection of their second Duchenne MD drug golodirsen was due to some concerns regulators raised about the risk of infection and the possibility of kidney toxicity. But when pressed to release the letter for all to see, he declined, according to a report from BioPharmaDive, saying that kind of move “might not look like we’re being as respectful as we’d like to be.”

He went on to assure everyone that he hadn’t misrepresented the CRL.

But Ingram’s public remarks didn’t include everything in the letter, which — following the FDA’s surprise about-face and unexplained approval — has now been posted on the FDA’s website and broadly circulated on Twitter early Wednesday.

The CRL raises plenty of fresh questions about why the FDA abruptly decided to reverse itself and hand out an OK for a drug a senior regulator at the FDA believed — 5 months ago, when he wrote the letter — is dangerous to patients. It also puts the spotlight back on Sarepta $SRPT, which failed to launch a confirmatory study of eteplirsen, which was only approved after a heated internal controversy at the FDA. Ellis Unger, director of CDER’s Office of Drug Evaluation I, notes that study could have clarified quite a lot about the benefit and risks associated with their drugs — which can cost as much as a million dollars per patient per year, depending on weight.

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How to cap­i­talise on a lean launch

For start-up biotechnology companies and resource stretched pharmaceutical organisations, launching a novel product can be challenging. Lean teams can make setting a launch strategy and achieving your commercial goals seem like a colossal undertaking, but can these barriers be transformed into opportunities that work to your brand’s advantage?
We spoke to Managing Consultant Frances Hendry to find out how Blue Latitude Health partnered with a fledgling subsidiary of a pharmaceutical organisation to launch an innovative product in a
complex market.
What does the launch environment look like for this product?
FH: We started working on the product at Phase II and now we’re going into Phase III trials. There is a significant unmet need in this disease area, and everyone is excited about the launch. However, the organisation is still evolving and the team is quite small – naturally this causes a little turbulence.

Wuhan virus out­break trig­gers in­evitable small-biotech ral­ly

Every few years, a public health crisis (think Ebola, Zika) spurred by a rogue pathogen triggers a small-biotech rally, as drugmakers emerge from the woodwork with ambitious plans to treat the mounting outbreak. In most cases, that enthusiasm never quite delivers.

Things are no different, as the coronavirus outbreak in Wuhan, China takes hold. There have been close to 300 confirmed human infections in China, and at least four deaths. Coronaviruses are a large family of viruses, which include MERS and SARS. On Tuesday, the CDC reported the virus was detected in a US traveler returning from Wuhan.

Brex­it fears, Wood­ford woes over­shad­owed UK biotech and cut 2019 fi­nanc­ing by al­most half

The venture tide might have subsided, the IPO window may be closing and certain listed biotechs may be having a tough time amid Neil Woodford’s well-publicized demised, but there’s still plenty to celebrate in the UK BioIndustry Association’s eyes.

Overall investment in UK biotech last year fell from the record-breaking £2.2 billion levels of 2018 to £1.3 billion — including £679 million in venture capital, a meager £64 million in IPOs plus £596 million when you add up all public financings, according to a new report from the BIA.

Blue­print Med­i­cines po­ten­tial­ly de­lays Ay­vak­it de­ci­sion; Con­trol beats treat­ment in mesothe­lioma tri­al

→ Blueprint Medicines filed an amendment to its application to get the gastrointestinal stromal tumor (GIST) drug Ayvakit approved in fourth-line GIST, the company disclosed in the prospectus for a new $325 million public offering.  Blueprint got a big accelerated OK on the drug this month in a particular mutation, but because the FDA decided to split their review in two, they didn’t hear on fourth-line GIST. They were supposed to hear before February 14, but this amendment could push that date back by 3 months. Blueprint wrote that the amendment is designed to allow the company to comply with the FDA’s request for data from the Phase III Voyage trial before they give a judgment.

Io­n­is, Akcea boost­ed by a pos­i­tive PhII for their No­var­tis castoff car­dio drug — and they plan to push ahead in­to piv­otals

Late last year Novartis abandoned a cardio drug from Ionis’ spinoff Akcea just after the pharma giant snapped up inclisiran, going the RNAi way in guarding against heart disease in the $9.7 billion Medco buyout.

Now the pharma goliath — which is headed down the PCSK9 road with a drug it believes can be used in a mass population — can get a clearer picture of just what they gave up.

Akcea $AKCA and the mother company $IONS put out a statement early Wednesday saying that their Phase II study of AKCEA-APOCIII-LR delivered solid efficacy data, with the high dose clearly outperforming placebo in significantly reducing triglycerides as a means to cutting the risk of cardiovascular disease. In addition, investigators concluded that the drug slashed apoC-III, very low-density lipoprotein and remnant cholesterol while boosting “good” HDL levels.

Hal Barron and Emma Walmsley, GSK

GSK’s ‘break­through’ BC­MA can­cer drug gets a pri­or­i­ty re­view — and a big win for the on­col­o­gy R&D team

After largely whiffing the past 2 years on the pharma R&D front, GlaxoSmithKline research chief Hal Barron has seized boasting rights to a key win that puts them back in the cancer drug development game.

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Who are the young bio­phar­ma lead­ers shap­ing the in­dus­try? Nom­i­nate them for End­points' spe­cial re­port

Update: Nominations open through end of day, Monday, January 27

Two years ago, when we did our first Endpoints 20-under-40, we profiled a set of up-and-comers who promised to help reshape the industry as we know it. Now we’re back and once again looking for the top 20 biopharma professionals under the age of 40. We’ll be profiling folks who have accomplished a lot at a young age but seem on the verge of accomplishing so much more.