Monday, September 17, 2018
DOJ clears Cigna deal with Express Scripts
Cigna (CI) announced that the Antitrust Division of the United States Department of Justice has cleared its pending merger with Express Scripts (ESRX). Shares of Aetna (AET), which has agreed to merge with CVS Health (CVS), are up 1% following Cigna’s announcement.
https://thefly.com/landingPageNews.php?id=2791567
JUUL Presents on Cytotoxicity Study at Tobacco Science Research Conference
JUUL Labs, Inc. today announced results from a preliminary study on the cytotoxicity of aerosol generated from JUUL’s Menthol, Mint and Cucumber 5% nicotine-e-liquid filled pods. The findings, “Neutral Red Uptake (NRU) Cytotoxicity Analysis of Aerosol Generated from a Temperature-Regulated Nicotine-Salt Based Ends Product,” were presented at a poster session at the 72ndTobacco Science Research Conference in Memphis, TN.
In accordance with the Organisation for Economic Co-operation and Development (OECD) guidelines, an independent contract laboratory, Enthalpy Analytical, measured and compared the toxicity to living cells of aerosol generated from JUUL’s Menthol, Mint and Cucumber 5% nicotine-e-liquid filled pods with that of tobacco cigarettes. The study demonstrated no significant aerosol toxicity at any of the observed concentrations for JUUL’s Menthol, Mint and Cucumber pods compared to a cigarette control.
“We are encouraged by the results of this study, in which tested aerosols generated from JUUL were not cytotoxic to living cells,” said Dr. Manoj Misra, study author and head of Toxicology at JUUL Labs. “These findings add to the growing body of evidence regarding use of JUUL as an alternative to combustible cigarettes, and we are committed to future rigorous, independent and peer-reviewed clinical trials and behavioral studies.”
Authors of the study include Dr. Manoj Misra of JUUL Labs and Drs. I. Gene Gillman and Pooja Desai of Enthalpy Analytical.
Argenx moves to make the most of its lead
Promising mid-stage data in a third indication for efgartigimod have given the Belgian company another boost.
Argenx’s efgartigimod is one of the leading projects to promise an alternative to decades-old therapies like plasma exchange and intravenous immunoglobulins. And, after announcing success in a mid-stage study in a third indication today, the Belgian company made it clear that it wants to win the race to market.
Having started a phase III trial in in generalised myasthenia gravis this month, Argenx today said it would push into pivotal trials in primary immune thrombocytopenia (ITP) as soon as possible. The mid-stage data in ITP were certainly encouraging, though having been generated in a small patient set the usual warnings apply.
Only topline data were released from the trial, which enrolled 38 patients with primary ITP. Response rates were encouraging, as the table below shows, and seem to compare favourably with one of efgartigimod’s biggest competitors, UCB’s rozanolixizumab.
Both projects work by reducing the levels of IgG circulating in the body, which is the goal of treatments for IgG-mediated autoimmune diseases like ITP. Both bind to FcRn (neonatal Fc receptor), which controls the recycling of IgG, though UCB has taken an antibody approach and Argenx is using an antibody fragment, specifically the Fc-portion of an IgG1 antibody.
Aside from the usual caveats of cross-trial comparison, it should be noted that the UCB study did not have a placebo arm; Argenx said the placebo response in its study was surprisingly high. On a conference call today this was blamed on one individual patient who had a dramatic and seemingly spontaneous rebound in platelet count that is virtually never seen.
| RACING TO MARKET? ITP TRIALS FOR FC-TARGETING PROJECTS | |||||
|---|---|---|---|---|---|
| Efgartigimod | Rozanolixizumab (interim results) | ||||
| 5mg/kg (n=6) | 10mg/kg (n=6) | Placebo (n=3) | 4 mg/kg (n=15) | 7 mg/kg (n=13) | |
| Clinically relevant improvement in platelet counts (≥50×109/l) | 46% | 46% | 25% | 53% | 31% |
| Source: Company press releases. | |||||
In the coming weeks UCB will unveil the final results from its trial of rozanolixizumab in ITP, which will include additional dosing groups. Both companies are expected to hold presentations at this year’s Ash conference in December, when investors should get a much clearer picture of these projects’ safety and efficacy profiles.
Potentially, however, UCB still holds an important card in this race. Rozanolixizumab is already being tested in a subcutaneous formulation, while efgartigimod will be delivered intravenously across its pivotal programme.
A subcutaneous formulation will enter phase II shortly, Argenx stressed today. But, if efgartigimod fails to demonstrate real safety or efficacy advantages over the UCB project, Argenx could find its pole position quickly eroded by a more convenient contender that is not that far behind.
Weighty expectations
For now, however, the sellside appears convinced that efgartigimod has a rosy future. Exuberant sellside analysts expect it to reach the market in 2020 and generate sales of $1.9bn by 2024, according to consensus data from EvaluatePharma – huge numbers to be attached to a project that has only recently gone into phase III.
Those forecasts equate to an NPV of $6.5bn, making efgartigimod the industry’s most valuable unpartnered asset, a recent Vantage analysis found (Most valuable unpartnered assets reveal a changing of the guard, August 14, 2018).
Investors are taking a slightly more cautious stance, but have still embraced the Argenx story pretty enthusiastically; the company’s market cap currently stands at $3.1bn.
Executives clearly believe that speed is of the essence here. Another contender from Syntimmune is also looking encouraging, so Argenx is right to be looking over its shoulder. But, with such huge expectations already attached to efgartigimod, Argenx cannot trip up in its rush to market.
| LEADING ANTI-FCRN ASSETS | |||
|---|---|---|---|
| Product | Company | Mechanism | Administration |
| Phase III | |||
| Efgartigimod (ARGX-113) | Argenx | Anti-FcRn Mab (fragment) | Weekly IV infusions tested phase III; subcutaneous phase II trials planned. |
| Phase II | |||
| Rozanolixizumab | UCB | Anti-FcRn MAb | Weekly subcutaneous doses tested in phase II. |
| Synt001 | Syntimmune | Anti-FcRn MAb | Weekly IV infusions tested in phase I/IIa. |
| Source: EvaluatePharma. | |||
Allogene spells out its interest in Cellectis
As Allogene moves to follow Autolus onto the public markets, its IPO document could give hope that Cellectis’s allogeneic assets will at long last make meaningful progress through development.
Since two big events a year ago, when Gilead bought Kite Pharma for $11.9bn and Novartis’s Kymriah became the world’s first CAR-T therapy, investors interested in cell therapy have had little to shout about. But now there are signs of a resurgence.
The latest came on Friday, as the team that sold Kite revealed that its new venture, Allogene, would seek a $100m flotation – barely five months after being founded. Allogene is now Cellectis’s key partner, and so investors in the French group should be poring over newly revealed information in the IPO document.
The most interesting details concern the pipeline assets on which Allogene will focus. Most of these date back to Cellectis’s initial alliance with Pfizer, focusing on the discovery of 15 antigens of which only BCMA and EGFRvIII had been disclosed.
Allogene, of course, took over Pfizer’s rights to this deal, as well as rights to Cellectis’s lead, UCART19, which Pfizer had licensed from Cellectis’s partner Servier (Pfizer washes its hands of Cellectis, April 3, 2018). Allogene’s IPO filing also reveals previously secret financial terms of this last tie-up.
| ALLOGENE PIPELINE | ||
|---|---|---|
| Antigen target | Asset | Detail |
| CD19 | UCART19 | Ongoing phase I trials in paediatric & adult ALL |
| CD19 | ALLO-501 | NHL; manufacturing differs from UCART19 |
| BCMA* | ALLO-715 | Multiple myeloma IND filing 2019 |
| Flt3* | ALLO-819 | AML, same target as Rydapt |
| CD70* | Unnamed | NHL & renal cell cancer, same target as cusatuzumab |
| DLL3* | Unnamed | SCLC, same target as Rova-T |
| CD52 | ALLO-647 | Lymphodepleting MAb, same target as Campath |
| Note: *Talen-edited, allogeneic CAR-Ts derived from 15-target alliance between Pfizer and Cellectis. Source: Allogene S-1 filing. | ||
As for targets, Allogene says it will continue to pursue BCMA, fast becoming a crowded space, and newly discloses a focus on Flt3, CD70 and DLL3, which are far less popular with CAR-T players. DLL3 is the target of Abbvie’s ill-fated Rova-T, so Allogene will hope that a CAR-T approach delivers better efficacy than an antibody-drug conjugate.
ALLO-501 is structurally identical to UCART19, but uses a different manufacturing process, while ALLO-647 seems to be an attempt to develop a better lymphodepleting chemo than Campath. It appears that the EGFRvIII asset is not being taken forward.
The IPO proceeds will primarily fund UCART19, an asset that has proceeded at a glacial pace since clinical trials began in 2016. If Pfizer had lost interest in UCART19 then Allogene’s involvement will be viewed positively, and investors will also note the light the IPO document sheds on the details of the 2015 deal under which Pfizer acquired rights to UCART19.
This asset had been optioned to Servier, and Pfizer outmanoeuvred Cellectis by licensing it directly from Servier once that company had exercised its option with Cellectis. Until now all that was known was that the exercise, announced on November 19, 2015, cost Servier $38.2m up front, plus $300m in milestones.
Allogene’s IPO document reveals that Pfizer’s end of the deal cost the US big pharma giant just $29m up front and $381.5m in milestones, making Servier’s acquiescence seem puzzling. Moreover, Allogene states that the Pfizer/Servier deal was done “in October 2015”, meaning that by the time Servier triggered the Cellectis option in November the asset was effectively already Pfizer’s.
Resurgence
Whatever the details, the fact that Allogene is already attempting to float is remarkable. The company was born with a huge, $300m series A financing round in April, and this month added $100m in private cash.
In June the UK CAR-T player Autolus floated in a $150m listing, and the relatively early development stage at which both companies are going public will raise eyebrows. That said, if this is the sign of a resurgence, then neither company should find it difficult to raise more cash on Nasdaq.
Much of the sentiment behind Allogene stems from Arie Belldegrun and David Chang, the management team that sold Kite to Gilead. Both now run Allogene, and have attracted numerous other key ex-Kite employees – though one, Margo Roberts, inventor of an important Kite patent and formerly chief scientific officer, passed up this opportunity and recently emerged as a director of Celyad.
The next move from another private cell therapy group, Tmunity, based on work at University of Pennsylvania and run by Oz Azam, former head of cell therapy at Novartis, is eagerly awaited.
Piper reiterates Overweight on Crispr after ViaCyte collaboration
Piper Jaffray analyst Edward Tenthoff reiterates an Overweight rating on Crispr Therapeutics with a $67 price target after the company announced a collaboration with ViaCyte. ViaCyte is developing the stem cell therapy for insulin deficiency, but is currently limited by host rejection, Tenthoff tells investors in a research note. He points out that Crispr will develop gene-edited immuno-evasive properties into the cells, a potentially curative therapy. The analyst believes the collaboration leverages Crispr’s gene-editing in diabetes.
https://thefly.com/landingPageNews.php?id=2791495
FDA approves first rescue stent to seal coronary artery tears in 17 years
The Berlin-based company plans to make the PK Papyrus covered stent available in the U.S. in 2019. (Biotronik)
Pfizer ‘all in’ on next-gen pneumococcal vaccine candidate: CFO
The race is on for a next-generation pneumococcal vaccine. Merck has already pushed its 15-valent candidate into phase 3, and on Thursday, Pfizer CFO Frank D’Amelio said his company is “all in” on reaching the market as soon as possible with its candidate.
At a Morgan Stanley healthcare conference Thursday, D’Amelio said after Pfizer closed its internal neuroscience program earlier this year, the company shifted resources to accelerate development for its 20-valent pneumococcal vaccine candidate. Pfizer believes it can enter the market at a competitive timeframe to Merck and its next-generation shot, D’Amelio said. Pfizer already markets pneumococcal vaccine Prevnar 13, the world’s bestselling vaccine.
On market entry timing, he said “if we are close, we think the strength of the current franchise,” plus additional protection, will allow Pfizer to retain market share and “keep the franchise growing very nicely.”
Pfizer recently completed a proof-of-concept study for its vaccine and “will start spending a bunch of money” to support its 20-valent candidate, the CFO said. Phase 2 data showed the vaccine can induce immune responses to all 20 pneumococcal serotypes, and that it was safe and well tolerated. The company is planning a phase 3 testing program.
Merck is already in phase 3 with its vaccine. In one late-stage study, Merck is testing its candidate head-to-head against Prevnar 13.
Last year, Pfizer’s Prevnar franchise generated $5.6 billion around the world, a 2% decline from 2016. Sales for the shot have flattened after fast growth in recent years, but D’Amelio said Pfizer believes it can still grow the franchise going forward due to opportunities outside of the U.S.
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