Kernel, a medtech company based in California, has developed the Kernel Flow, a wearable helmet that can perform time domain functional near-infrared spectroscopy (TD-fNIRS) imaging of the brain. The system has a smaller footprint, is less expensive and less complex than benchtop TD-fNIRS systems, but has demonstrated similar imaging performance. The imaging modality measures changes …
Alnylam executives are heralding the replication of data between approved medicine Onpattro and the investigational treatment vutrisiran, which the company is trying to position as an easier-to-administer, next-generation treatment for transthyretin-mediated (ATTR) amyloidosis.The FDA is already considering vutrisiran for approval in ATTR amyloidosis, a rare and fatal disease that occurs in people born with TTR gene mutations that cause the liver to produce abnormal, often misfolded TTR proteins. The decision date for the therapy is April 14.
As Alnylam awaits the decision, the new late-stage data from month 18 helps pad the case for approval. Analysts, however, noted a few subtle differences where vutrisiran differed from the approved medicine.
The phase 3 Helios-A study included 164 patients with hereditary ATTR amyloidosis with polyneuropathy. Patients received either vutrisiran or Onpattro. Vutrisiran met all the primary endpoints in the test, though that was based on comparing results from the vutrisiran arm to those from the placebo group of an earlier phase 3 Onpattro trial called Apollo.
Helios-A’s main goals centered around improvements in neuropathy impairment, quality of life, gait speed, nutritional status and overall disability. The trial and Apollo reportedly have similar patient populations.
RELATED: Alnylam’s next-gen ATTR amyloidosis drug hits goals in phase 3, teeing up approval filing
When compared to Onpattro, vutrisiran was found to be noninferior in terms of serum transthyretin reduction. In ATTR amyloidosis, reduction of TTR serum is a known biomarker of the disease.
Vutrisiran was also successful in an exploratory cardiac endpoint in the study, which included a known biomarker of heart failure called NT-proBNP. Safety and tolerability was consistent with data reported at the nine-month mark.
Alnylam already has Onpattro approved in a type of ATTR amyloidosis and is investigating it in another subtype. The company reported during the J.P. Morgan Healthcare Conference last week that 2,050 patients are now taking Onpattro.
If vutrisiran is approved, the pool of patients could expand to 30,000 to 40,000, according to Rena Denoncourt, Alnylam VP and TTR franchise lead.
RELATED: BridgeBio’s ‘baffling’ heart disease drug fail ‘de-intensifies’ competition for Alnylam
But some analysts, during a Friday morning conference call, pointed to a few points in the data release where vutrisiran differed from Onpattro. This included a question about the maintenance of serum reduction at month 18, which seemed to dip compared to what was seen at month nine.
President Akshay Vaishnaw pointed to the challenges of replicating data across studies and said the Helios study was an “important replication of Apollo.”
“It’s a remarkable replication of data across different studies, and minor differences here or there…when you look at the overall picture, it’s striking and patients have improved in their neuropathy,” Vaishnaw said.
Alnylam announced nine-month data on vutrisiran a year ago, showing that the treatment met the main goal of the Helios-A trial of improving neuropathy impairment, but the release lacked the crucial comparative data with Onpattro.
Patients taking Onpattro have to undergo an 80-minute infusion every three weeks, meaning there’s plenty of room for a treatment with a less onerous dosing schedule. Alnylam is trying to position vutrisiran as just that, with doses delivered via subcutaneous injection every three months.
RELATED: JPM22: Intellia stacks ATTR trial with new patient group, will weigh later-stage tweaks after BridgeBio setback
If approved, Alnylam would have an even tighter grip on the ATTR amyloidosis market, a disease that has been in the news several times over the past few weeks. Alnylam’s competitor in this space, BridgeBio, suffered a phase 3 setback in late December when its candidate acoramidis failed to beat placebo on a six-minute walk test.
The BridgeBio results have sent a ripple through the ATTR treatment community, with analysts wondering how an ongoing trial of Onpattro that features the same six-minute walk test as a goal might fare.
Gene editing biotech Intellia, which presented first-in-human gene editing data in the disease back in June, announced an acceleration of its clinical program to a broader group of patients during the J.P. Morgan conference. The company is considering whether some tweaks need to be made to the endpoints in future late-stage trials after the BridgeBio news.
Vutrisiran has been filed for approval in the U.S., EU, Brazil and Japan.
Yingli Pharma has tapped MD Anderson Cancer Center to support its U.S. expansion. The collaboration sets Yingli up to run a raft of clinical trials in the U.S. to build on data generated on its cancer candidates in China.Working out of Shanghai, Yingli has built an oncology pipeline led by PI3Kδ inhibitor linperlisib that has come through eight phase 1 and 2 clinical trials in patients with lymphomas and solid tumors. Linperlisib is in phase 3 in follicular lymphoma, and, with other candidates following it down the pipeline, Yingli has decided now is the time to start trying to bring its drugs to the U.S.
MD Anderson has signed up to support the effort. Under the terms of a five-year collaboration, the Texas cancer center will work with Yingli to start a phase 2 clinical trial of linperlisib in patients with peripheral T-cell lymphoma (PTCL). In a statement, MD Anderson’s Swaminathan Iyer, M.D., the principal investigator, called the candidate a “potentially effective treatment option with a favorable safety profile.”
Chemotherapy combinations are the go-to initial treatment for most subtypes of PTCL, but, with many people advancing after first-line treatment, there is a major need for drugs that are effective in relapsed and refractory patients. Developers of other PI3K inhibitors including Bayer and Secura Bio have explored the efficacy of their molecules in PTCL, and Yingli looks unlikely to be the first to market in the U.S..
RELATED: MD Anderson, RaySearch ally to take adaptive radiation therapy mainstream
Yingli also plans to work with MD Anderson on a phase 1 solid tumor clinical trial of its oral TGFβR1 inhibitor YL-13027. The trial, which is set to start this year, will provide an early look at whether the drug lives up to its billing as a differentiated, potentially more effective inhibitor of a signaling pathway that companies including Eli Lilly have gone after without success.
The partners will also perform translational work on Yingli’s pipeline of earlier-stage prospects, which includes an inhibitor of KRAS G12C, a cancer mutation targeted by companies including Amgen and Mirati Therapeutics.
Kura Oncology is back in the game. Two months after the FDA sidelined its blood cancer trial in response to a patient death, Kura has had the partial clinical hold lifted, clearing it to resume the screening and enrollment of new patients.
San Diego-based Kura told investors to expect a short pause when the FDA imposed the partial hold back in November, reflecting a belief the agency’s request for information would be relatively simple to meet. Just under two months later, Kura has delivered on its vow to work quickly through the setback and is now ramping activities up again.
“Activities to resume patient screening are underway, and we look forward to expediting enrollment of patients in the phase 1b study and determining the recommended phase 2 dose for KO-539 in the coming months,” Kura CEO Troy Wilson said in a statement.
The FDA lifted the partial clinical hold after it reached an agreement with Kura on a mitigation strategy for differentiation syndrome, the adverse event implicated in the death that triggered the restrictions. Differentiation syndrome is a known adverse event of differentiating agents, a class that includes KO-539 and approved drugs such as Agios Pharmaceuticals’ Tibsovo, used in acute myeloid leukemia (AML).
RELATED: FDA halts phase 1b Kura Oncology trial in acute myeloid leukemia following patient death
While KO-539 shares some similarities with existing molecules, its targeting of a menin protein-protein interaction gives it a novel mechanism of action that Kura expects to have anti-tumor activity in around one-third of AML patients. Kura is initially developing KO-539 as a monotherapy in those genetic AML subtypes but also sees opportunities to enter earlier lines of therapy in combination with other drugs.
The lifting of the partial clinical hold positions Kura to resume work toward those opportunities. Kura was enrolling phase 1b expansion cohorts before the partial clinical hold to determine whether to take the 200-mg or the 600-mg dose into a registration-enabling phase 2 study.
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Researchers at Northwestern University developed a nanoparticle delivery system for a common immunosuppressant drug that increases the potential of pancreatic islet transplantation as a viable long-term treatment for Type I diabetes. The technology targets the drug to act on the antigen presenting cells of the immune system, rather than T cells. This results in a …
Hongming Chen has ended her long affiliation with Kala Pharmaceuticals. Having been with Kala since its origins in 2010, Chen has left the chief scientific officer post to become head of R&D at a biotech that is just starting out. Metis Therapeutics put itself on the map late last year, when it revealed $86 million in series A funding from backers including PICC PE, China Life and Sequoia Capital China. The financing set Metis up to take a drug candidate into the clinic in 2022 and in-license programs, from early-stage discovery to the cusp of human testing, that are a good fit for its artificial intelligence platform.
Now, Metis has added Chen to its roster. In appointing Chen as president and head of R&D, Metis has tasked its new recruit with leading the expansion of its U.S. operations and helping take early-stage programs through development and into the clinic.
Chen has experience of those R&D activities from her time at Kala. Over more than a decade at Kala, Chen rose to the rank of CSO and supported a pipeline that delivered FDA approvals in 2018 and 2020. While Kala succeeded in getting products to market, it failed to live up to the expectations of investors, causing its share price to fall from $25 shortly after its IPO in 2017 to less than $1 today.
RELATED: Metis Therapeutics emerges with $86M for 2022 clinic entry, push into gene therapy
Metis is too young to know such woes. The startup grew out of chats between CEO Chris Lai and MIT researchers in 2017 but only made waves late in 2021, when it disclosed the series A round. Metis is still playing its cards close to its chest, revealing little beyond the fact it is expanding its AI platform beyond small molecules and RNA therapeutics and into CRISPR tools and gene therapy.
Chen has slotted into a scientific leadership team that features Tolga Baykal, M.D., Ph.D., formerly of Regeneron, in the global clinical development post, Jeff Warrington, Ph.D., as director of medicinal chemistry and Takayo Inoue, Ph.D., at the head of the clinical pharmacology unit.
Kenneth Galbraith has made an immediate mark on Zymeworks. Days after taking up the CEO position, Galbraith has axed half the senior management team and disclosed plans to cut total headcount by 25%.Zymeworks disclosed the CEO transition Jan. 5, at which time it expected Galbraith to take up his new post by the start of February. Galbraith arrived well ahead of schedule and acted fast, assuming the role Jan. 15 and culling colleagues in his first week in the job.
The cull leaves Zymeworks with a new-look, slimmed-down management team. Tony Polverino, Ph.D., is among the high-profile casualties of the changes. Polverino joined Zymeworks from Kite Pharma in 2018 to work as chief scientific officer and executive vice president of early development. Zymeworks hired Polverino to set up and drive its R&D strategy and to manage the transition of drug candidates into early clinical development.
With its cash reserves running down, Zymeworks has now decided it can do without those skills, pushing Polverino out of the door along with its former chief people officer, chief commercial officer and half the senior leadership team. The exits are a precursor to a wider bloodletting that will see Zymeworks reduce its headcount by 25% by the end of the year.
RELATED: Zymeworks’ first CMO steps aside
Zymeworks had 455 full-time employees as of the end of September, suggesting 100 people or so will lose their jobs. The cuts follow a period of fast expansion. Zymeworks ended 2020 with 352 full-time employees. Returning back toward that size could help Zymeworks cut its cash burn, which topped $50 million a quarter in recent results, and thereby eke out the $250 million it had in the bank at the end of last year.
The remaining money, which Zymeworks expects to last “through at least late 2022,” will fund work on HER2-targeted bispecific antibody zanidatamab, which is in pivotal trials in biliary tract and esophageal cancers, and early-phase bispecific HER2‑targeted antibody-drug conjugate ZW49.
Responsibility for taking the assets forward will fall on a new-look leadership team. The changes leave Neil Josephson, M.D., who was promoted to chief medical officer last year, and Kaycia Wilde, Ph.D., VP of clinical operations, among the key people on the development side. Zymeworks plans to add a head of R&D to the team in the future.
Eli Lilly is so serious about becoming the leader in Alzheimer’s disease with donanemab that, last year, the Indianapolis Big Pharma challenged competitor Biogen by launching a head-to-head trial comparing their two therapies.So what gives the company the confidence? Lilly CEO David Ricks knows it’ll win.
“If you’re going to take on … the leader, you need to be the leader, and that’s the purpose of this experiment,” Ricks said during an executive interview for Fierce JPM Week.
This is a marked shift in thinking around Alzheimer’s research after decades of failures and disappointment. Lilly’s own scientists and even their now-prized candidate donanemab have been at the forefront of the long-fraught hunt for a disease-modifying treatment for the devastating neurological disorder.
RELATED: ‘What it takes’: As Lilly’s Alzheimer’s drug approaches FDA, launch leader feels ‘amplified’ sense of excitement
Now, Ricks says Lilly has a treatment that can address the underlying cause of the disease, and the regulatory path has been cleared thanks to Biogen and Eisai’s Aduhelm. That therapy was approved by the FDA last year based on biomarker data that suggested it could clear beta amyloid plaques, which are a hallmark of the disease. But the world still awaits proof of clinical efficacy in terms of changing the course of the disease, which Biogen will have to show in a phase 4 confirmatory trial. That study is slated to get underway this year.
Ricks says Lilly has proven donanemab can clear the amyloid plaques “in a very assertive way” in a clinical study. At six months, about half of patients had no detectable plaques in brain scans.
Eli Lilly’s donanemab will challenge Biogen’s Aduhlem in a head-to-head phase 3 trial this year. (Biogen)
“A lot of analysts say, ‘Why are you running it? You’re gonna win it automatically,’” Ricks said. “The confidence is pretty high in the company and maybe even higher outside of it.”
The phase 3 head-to-head trial, called TRAILBLAZER-ALZ 4, will rely on PET imaging to determine plaque clearance, which Ricks said provides a precise measurement that moves away from impressions of disease status that are determined by a doctor. This traditional method of assessing dementia can be problematic in a clinical trial as patients can be assessed as further along than they really are, or they had a particularly bad day when the assessment was conducted.
RELATED: Eli Lilly’s Alzheimer’s moment has arrived after Biogen plows through the FDA gates
“PET scanning and using analytical tools to define who gets into the study and then how they progress has turned out to be a much better way to assess drug performance,” Ricks said. “From the PET scans that have been indirectly done between the two drugs, we’re highly confident that at six months we will have cleared more plaque than them.”
Another way Lilly hopes to best Biogen and Eisai is in the launch. Aduhelm has hit roadblock after roadblock, the latest being the Centers for Medicare & Medicaid Services (CMS) decision to limit coverage to clinical trial participants.
In a bit of support for Biogen, Ricks called the CMS decision “a mistake” and one that will limit demand for anti-amyloid therapies and make patient access even harder. That means Lilly will have to work hard to launch donanemab and communicate its benefits to patients.
RELATED: Eli Lilly kick-starts speedy FDA review for Alzheimer’s hopeful donanemab—and a one-on-one test against Aduhelm
Lilly is expecting an accelerated approval from the FDA sometime this year. Donanemab demonstrated a 32% slowing in disease during an earlier phase 1 study, according to Ricks, and the company hopes to see similarly strong results this year for the late-stage test.
“If we come up with something like that, in phase 3, I think that’ll be an impressive and important part of the introduction,” he said.
At the end of Jay Bradner’s interview for Fierce JPM Week, the Novartis innovation chief turned to the camera and implored small biotechs to get in touch to talk M&A or potential partnerships.“Please reach out, please don’t presume even though the market is showing a decline in large cap M&A,” Bradner, M.D., said. “There’s never been a better time to do earlier stage partnering.”
And Bradner would know. He’s now the president of the Swiss pharma’s innovation engine, Novartis Institutes for BioMedical Research (NIBR), but he cut his teeth in biotech. He co-founded five biotechs before landing at Novartis in 2016.
“When you’re halfway through an A round—even the big ones that are raised today—people start to get really pragmatic,” he said. “And being out in the public markets, exposed with preclinical programs, I think can create an appetite for real partnering.”
RELATED: Novartis doesn’t think optogenetics will completely cure blindness—but its new biotech is going to give it a try
Bradner specifically noted companies involved in genome engineering, next-generation biologics, molecular glues and protein degradation.
“Through partnership with NIBR, I think there’s quite a lot that we can do together. So please do reach out—and don’t read through any lack of ambition or interest in partnering, especially at this important time,” said Bradner.
With that invitation, though, Bradner made clear earlier in the interview that Novartis is looking for real innovation, not next-generation therapies that redo existing medicines.
“We absolutely have a real hungry appetite to do deals, whether they’re early-stage partnerships or partnerships to bring later-stage assets to patients around the world through the intergalactic capabilities of our global pharmaceutical company,” Bradner said. “I can assure you that the demand and appetite is there.”
The pharma giant does not want to follow its peers into oversaturated fields to create follow-on therapies. He attributes the presumed lack of interest in M&A to two themes that he saw play out over 2021.
RELATED: Novartis sharpens focus on vision-restoring gene therapy with $150M Vedere buyout
“The first is—I hate to say it—a lack of over jaw-dropping innovation,” according to Bradner. “Though there’s never been a more exciting time to practice drug hunting, there’s quite a lot of fast follower research out there on the outside, and we internally prioritize our resources for first-in-class—maybe almost to our own detriment.”
Bradner says that as pharmaceutical companies “scurry around to gobble up me-too assets,” deal demand is being driven by large investments in “thinly differentiated next-generation products.”
Novartis does not want to play in that sandbox, which leads to Bradner’s second point: The biotechs that are interesting are just too expensive at the moment. This is also driven by the rise in nontraditional investment that has provided plenty of early-stage capital without the need for Big Pharma backing.
The COVID-19 pandemic catapulted interest in biotech investing, leading large pharmaceutical companies to pull back on acquiring new medicines, especially from publicly traded companies, according to Bradner. To buy a public company—which in biotech is happening earlier and earlier in a startup company’s life span—Novartis and its peers have to pay a premium to the stock price.
RELATED: JPM 2022: Licensing and research tie-ups trump M&A at conference in ‘reflection of last year’
All that said, Novartis is prepared to splurge: “There’s a small number of assets that we’re gonna go after, even though they’re priced up.”
So what companies could Novartis be interested in? Bradner, of course, would not say, but he pointed to the pharma’s recent track record as an indication of where it may go. He specifically flagged the “unicorn” Zolgensma, which in 2019 became one of the first gene therapies on the market and treats spinal muscular atrophy.
Two other acquisitions can provide clues: optogenetics-focused Arctos Medical, which joined the similarly focused Vedere Bio last year under Novartis’ wing. Vedere was a $150 million bolt-on, while financial terms for Arctos were not disclosed.
Bradner is one of the pharma industry executives mourning the loss of the in-person J.P. Morgan Healthcare Conference event, where chance meetings can lead to the exact type of dealmaking he’s looking for.
“Maybe I’m just an old-fashioned Midwesterner, but I really value face-to-face, shoulder-to-shoulder innovation,” he said.
RELATED: 2022 forecast: Biopharma M&A lags in 2021. Will drugmakers still look for bolt-on deals or large transactions?
So while virtual meetings and Zoom conferences are efficient, he can’t wait for the opportunity to get back on the ground. Even so, meetups are continuing to happen, thanks to Novartis’ partnering initiatives and the company’s venture fund.
“We’ve probably never been easier to find and to connect with, where travel or walking up the big hill to the hotel we occupy at JPM are no longer barriers,” Bradner said.
Researchers at Cambridge and Bath universities in the UK, along with colleagues at the Ifakara Health Institute in Tanzania, have created two devices, called autohaem, that assist in creating blood smears, a common technique for diagnosing malaria. A blood smear involves manually smudging a drop of blood across a microscope slide to allow observation of …