JP Morgan Day 4: Immunomedics

Immunomedics (IMMU) is on the cusp of its first approval with the PDUFA date for sacituzumab
govitecan in metastatic triple negative breast cancer (mTNBC) set for 18 January 2019. As a small
company handling its first launch, management were keen to show that they are “launch ready”,
discussing the company’s operations and supply chain as well as partnerships it has made with
Samsung Biologics, Johnson Matthey, and BSP Pharmaceuticals to enable supply in case of
growing demand due to subsequent approvals. Immunomedics is in a strong cash position with
$583m cash and no long-term debt.
In terms of sacituzumab govitecan’s potential in mTNBC, the company outlined strong Phase II
data in which the therapy provided an overall response rate (ORR) of 33% and a progression-free
survival of 5.5 months, which compare well to data from other therapies for similar patient
groups. Head-to-head trial data is not yet available, though a Phase III comparative trial is
underway. Sacituzumab govitecan is under regulatory review for the treatment of mTNBC
patients who have received two prior therapies; this is a patient group who have few options and
where sacituzumab govitecan will likely be well-received. Indeed, the company stated its
intention to make sacituzumab govitecan the standard of care for third-line treatment.
The majority of the company’s remaining pipeline activity comprises of investigating sacituzumab
govitecan in other indications. A pivotal Phase II trial in advanced urothelial cancer was initiated
in June 2018, a pivotal Phase III trial in HR+/HER- breast cancer is planned for the first half of
2019, and a non-pivotal basket study investigating sacituzumab govitecan for refractory nonsmall cell lung cancer, small cell lung cancer, head and neck squamous cell carcinoma, endometrial cancer, and hepatocellular carcinoma is planned for the second half of 2019. With a ikely launch and a busy clinical program, 2019 should be a good year for Immunomedics.

http://images.intelligence.informa.com/Web/InformaUKLimited/%7Ba9dcc568-c28c-450e-a678-60ab0dbb2304%7D_JP_Morgan_2019_-_Day_4.pdf

Aeterna Zentaris gains

Aeterna Zentaris up 7% in early trading  The move higher may be related to tweets claiming that the company received an approval in Europe, according to contacts.
https://thefly.com/landingPageNews.php?id=2847635

Weight Watchers Hit on JPMorgan Downgrade

Shares of Weight Watchers International Inc.  (WTW – Get Report) fell 8.3% to $32.16 Friday after JPMorgan analyst Christina Brathwaite downgrades the weight management services company to neutral from overweight with a price target of $37.

Brathwaite said in a research note that she was “throwing in the towel” as early channel checks point to a weak 2019 start for the business. She said that she believed traffic to the company’s website and engagement on its mobile app are down double-digits year-over-year, which could indicate that new member growth will likely start 2019 at a slower pace than previously anticipated.

Braithwaite said Weight Watchers had announced at the beginning of 2017 a long-term target of achieving more than $2 billion in revenue by the end of 2020.

“While it’s still very early in the New Year Resolution season and (Weight Watchers) could make up for the shortfall in the coming months (particularly as some of the shortfall may be related to the government shutdown as furloughed workers are less likely to start a diet membership),” Braithwaite wrote, “we believe current trends will make it difficult for the company to generate significant growth in members, with our checks indicating new weight loss brand Noom may be siphoning traffic from (Weight Watchers).”

Noom is a new mobile app weight loss program, Braithwaite said, which includes enhanced personalization by assigning each member a “health coach” who answers questions, provides tips, and helps keep members on track towards goals.

In November, Weight Watchers, which recently changed its name to WW, posted third-quarter net income of $70.1 million, or $1 per share, up from $44.7 million, or 65 cents, a year ago. Revenue totaled $366 million, up 14% from a year ago, but missed analysts’ expectations of $379 million.

The company said it ended the third quarter with 4.2 million subscribers– up 25% year over year, but that number fell from 4.6 million subscribers in the first quarter and 4.5 million in the second quarter.

At that time, CFO Nicholas Hotchkin said during a conference call with analysts that, historically, about 40% of the company’s annual member recruitments have occurred during the first quarter. Therefore, Hotchkin said, “each year first quarter is our peak for end of period subscribers and each year end is our low point.”

https://www.thestreet.com/investing/weight-watchers-sinks-on-jpmorgan-downgrade-14831501

Tilray Gains After Privateer Holdings Vows to Hold Stake Until At Least H2 2019

Tilray Inc. (TLRY) shares surged Friday after its biggest stakeholder said it would hold onto shares of the Canadian cannabis company until at least the second half of the year.

Privateer Holdings, a a Seattle-based private equity group that limits its investments to the cannabis industry that owns an estimated 76% of Tilary’s outstanding shares, said it has a strong belief in Tilray’s long-term global growth strategy and its “pioneering role” in shaping the future of the legal marijuana market.

“We do not have plans to register, sell or distribute the shares Privateer holds in Tilray during the first half of 2019,” Privateer managing partner Michael Blue said in a statement. “When we decide to distribute shares, we will do so in an orderly and deliberate manner to maximize tax-efficiency considerations for Privateer investors, while also taking into consideration potential impacts on Tilray’s public float. And we will do it in a way that reflects our long-term confidence in Tilray’s business model and management team.”

Tilray shares were marked 24% higher at the start of trading Friday and changing hands at $99.67 each, the highest since December 4.

Last month, Tilray and AB InBev’s BUD unveiled a new research partnership that will explore non-alcoholic beverages that contain THC and CBD, both key chemicals found in marijuana but with very different purposes.

THC is the psychoactive chemical in marijuana the produces the high, while CBD is non-psychoactive and blocks the high.

As part of the deal, each company will pitch in $50 million, with Tilray taking part through its subsidiary, High Park Co., which develops, distributes and sells cannabis products in Canada.

Bill Newlands, the incoming CEO of Corona Beer market Constellation Brands STZ, called the global cannabis market “the most significant global growth opportunities of the next decade, and frankly, our life time” adding that it was “opening up much more rapidly than originally anticipated.”

Constellation Brands rebounded from a two year low Thursday after weaker-than-expected quarterly earnings and a muted outlook pegged to rising costs associated with its $4 billion investment in cannabis specialists Canopy Growth Corp. (CGC)

https://www.thestreet.com/investing/stocks/tilray-surges-after-privateer-holdings-vows-to-hold-stake-until-at-least-h2-2019-14831335

Denali taps Sirion to expand into CNS gene therapies

Denali Therapeutics is teaming up with Sirion Biotech to expand into gene therapies. The partners will work to develop adeno-associated virus (AAV) vectors capable of crossing the blood-brain barrier.

Germany’s Sirion has landed deals with companies including Acucela and Orchard Therapeutics on the strength of its expertise in the manufacturing and delivery of gene therapies. That expertise extends to the design of AAVs, a group of gene therapy delivery vectors that have emerged as the preferred option for drugs designed to trigger the production of therapeutic agents in the brain.

Now, Denali has identified Sirion as the company to support its expansion into gene therapies. Denali will work with Sirion and the German company’s partner at the University Hospital Heidelberg, Dirk Grimm, to develop new and modified AAV capsids.

The goal is to develop AAV capsids that get across the blood-brain barrier and to targets in the central nervous system with greater specificity and efficiency than is possible with current vectors. Equipped with such vectors, Denali could develop gene therapies capable of getting the brain to make therapeutic levels of molecules to treat diseases including Alzheimer’s and Parkinson’s.

The potential for gene therapies to modify the brain so that it produces its own treatments, rather than try to get large molecules across the blood-brain barrier, has attracted companies including Novartis and Johnson & Johnson.

Denali, in contrast, has focused on small molecules and biologics since it burst onto the scene led by a team of ex-Genentech staffers in 2015. Since then, Denali has raised big sums of cash from private and public investors, enabling it to advance several candidates into clinical development and build a deep pool of preclinical programs.

The Sirion pact gives Denali the chance to add another modality to its pipeline and thereby increase the likelihood that it will be at the leading edge of efforts to treat neurodegenerative disorders in the coming years.

https://www.fiercebiotech.com/biotech/denali-taps-sirion-to-expand-into-cns-gene-therapies

Anti-aging startup Elevian enlists Insilico on AI quest for ‘young blood’

Some of the earliest connections Alex Zhavoronkov has built for his AI shop at Insilico Medicine involves marrying anti-aging and AI research, two of the buzziest areas in drug development. He’s now doubling down on it with a new R&D partnership with “young blood” startup Elevian.

The collaboration is aimed at developing oral medications targeting the GDF11, or growth differentiation factor 11, pathway and associated targets — a concept that Elevian has been working on since inception. Elevian is supplying the biological and structural target data that Insilico will use to identify small molecules via its generative adversarial networks (GANs) and reinforcement learning (RL) AI technologies.

Drawing inspiration from existing libraries of compounds — to be screened virtually and biologically — the scientists will then build (virtual) compound candidates to be synthesized by WuXi AppTec, an early collaborator and backer of Insilico.

The new partners share a connection in Peter Diamandis’ — of X Prize fame — BOLD Capital Partners, which invested in both companies.

In a similar deal inked last August, Insilico was recruited to develop tech out of the Buck Institute for Research on Aging on behalf of Napa Therapeutics, a spinout of the billionaire-backed startup Juvenescence (and another Insilico investor). The work is in nicotinamide adenine dinucleotide (NAD+) metabolism, with Napa holding rights to the tech and IP from the institute.

https://endpts.com/anti-aging-startup-elevian-enlists-insilico-on-ai-quest-for-young-blood/

Existing drugs may be able to strangle building blocks of metastasis

Metastatic disease is overwhelmingly responsible for cancer-related deaths, accounting for 90% of fatalities. Using existing drugs, researchers at the University of Basel may have found a strategy that stifles the spread of malignant circulating tumour cells (CTCs), the harbingers of the spread of cancer.

In the mid 19th century Australian pathologist Thomas Ashworth hypothesized that CTCs — cancerous cells that break away from a primary tumor and enter the bloodstream — were a fundamental prerequisite to metastasis. But isolating them was a big challenge, akin to the proverbial needle in a haystack as they are extremely rare, even in patients with advanced metastatic cancers (estimated at one CTC/billion normal blood cells), although recent technological advances have allowed for their detection, the Basel-based researchers noted in the journal Cell.

While Nicola Aceto worked as a postdoctoral fellow at Harvard Medical School, he found that circulating tumor cell clusters — not single cells — are typically the culprits with the firepower to trigger metastasis.

Aceto then spearheaded the formation of the Cancer Metastasis Lab at the University of Basel, leading a team of researchers who found that these clusters can mimic certain properties of embryonic stem cells, including the ability to proliferate and develop into tissue. However if these clusters are dissociated, these properties could be vanquished, they found, which prompted the search for substance that can quash such metastasis development by dissociating CTC clusters.

”We thought of acting differently from standard approaches, and sought to identify drugs that do not kill cancer cells, but simply dissociate them,” Aceto said in a statement.

The researchers used technology from UK-based ANGLE to identify clusters in patient blood, and consequently patients whose cancer would likely spread. In a study with mice, the team then tested 2486 FDA-approved drugs to ascertain their impact on breaking up these CTC cell clusters into individual cells. A small group of drugs were found capable: Treated mice experienced an 80% reduction in metastasis compared with untreated animals, with the metastatic spread of cancer virtually eliminated in treated animals.

The team is now expecting to test the chosen drugs in patients with breast cancer — a form of cancer that easily metastasizes — in a clinical trial this year. The approach of preventing metastasis instead of indiscriminately killing cancer cells, if successful, could potentially prove an improvement in terms of toxicity and side-effect profile versus conventional treatments such as chemotherapy and immunotherapy, the scientists say.

https://endpts.com/early-research-suggests-existing-drugs-could-strangle-building-blocks-of-metastasis/