JP Morgan 2018 - your essential guide to the key stories from pharma’s biggest investor conference - part 2
bluebird bio | Sanofi | Bristol-Myers Squibb | GlaxoSmithKline, Juno Therapeutics | Amgen | Nektar Therapeutics
bluebird bio was the early draw at day two of the JP Morgan Healthcare conference thanks its positioning at the intersection of gene and CAR-T therapy, with impressive clinical data recently presented in both fields.
It is the latter - focused initially on bb2121 in multiple myeloma - which is likely to bring the commercial success that will fuel longer term R&D investment and echoing sentiment expressed at ASH in December, CEO Nick Leschly suggested that studying the therapy in earlier-lines of therapy (potentially with a view to redefining which first-line patients eligible for a transplant) will happen at pace, with partner Celgene heavily focused on this goal. Leschly suggested there was no better partner for bb2121, citing Celgene’s current role in exploring surrogate endpoints as a means to expedite earlier line therapy.
In terms of near term revenue growth for Sanofi, it is hard to look to far beyond Dupixent, as excellent a commercial prospect the atopic dermatitis therapy is. The antibody, co-developed and commercialised with Regeneron, dominated Sanofi’s presentation on Tuesday, although much of this focus was sharpened on planned expansion into other indications, including potential approval in severe asthma later this year and initiation of pivotal-stage studies in chronic obstructive pulmonary disorder (COPD).
Echoing comments about continued emergence of the PD-1 inhibitor cemiplimab - made by Regeneron on Monday - CEO Olivier Brandicourt suggested it could also be an important year for Sanofi’s oncology pipeline. In addition to filing cemiplimab for cutaneous squamous cell carcinoma (cSCC), it will submit the anti-CD38 antibody isatuximab for relapsing remitting multiple myeloma and initiate pivotal-stage studies in first-line MM patients later this year. Brandicourt summed up Sanofi’s strategic priorities by outlining three core areas of transition; an increasing focus on biologics at the expense of small molecules, a focus on modes of action which are multi- rather than mono-targeting and continued development of proprietary technology platforms to reduce a historical dependency on externalisation.
Faced with intense competition in the immuno-oncology market, Bristol-Myers Squibb believes broader is better. Its clinical programme in first-line non-small cell lung cancer is testament to this, management boasted and the suggestion during Tuesday’s breakout session was that triple combinations comprising Opdivo (PD-1), Yervoy (CTLA-4) and an IDO inhibitor could soon move into the clinic for various tumour types. The hope being that this approach may prove critical in reducing disease resistance.
CEO Giovanni Caforio also revealed a new addition to Bristol-Myers Squibb’s early-stage R&D pipeline; a potential first-in-class selective, oral inhibitor targeting Tyk-2. This dual mechanism of action modulates two validated pathways in IL-12/IL-23 (inflammatory bowel disease, psoriasis and psoriatic arthritis) and interferon-alpha/beta (lupus) and offers a targeted profile which could be applicable across multiple immune disorders, said Caforio. Ideally, this Tyk-2 inhibitor will offer biologic-like efficacy with oral dosing and tolerable safety. Initial proof of concept has now been established in psoriasis, he confirmed.
CEO Emma Walmsley was forced to play something of a balancing act during GlaxoSmithKline’s breakout session on Tuesday; yes, the company will cast a speculative eye over Pfizer’s consumer healthcare unit as a possible acquisition, but this neither confirms that GlaxoSmithKline needs to bulk out its consumer business (nor will overpay) or indicates the pharmaceutical division is not the priority focus, she told investors.
Indeed, with both Hal Barron and Luke Miels in attendance - newly installed as GlaxoSmithKline’s chief science officer and pharmaceuticals president, respectively - Walmsley talked up the "dream team," she has assembled ahead of a crucial 12 month period which could validate the company’s R&D aspirations.
Barron looks to be the real coup and Walmsley promised an update from him later in the year (he has been in the job for little more than a week). Asked what had convinced him to join GlaxoSmithKline, Barron professed a long standing aspiration to head up a big pharma R&D organisation. He conceded, however, that the challenge - rather than GlaxoSmithKline’s pipeline - was his primary motivation.
Having just become the first female CEO to present in the grand ballroom at the JP Morgan Healthcare conference, Walmsley spoke of the privilege and responsibility of her role. Representing diversity does not stop at gender, she added, and she called on the industry to be more proactive, suggesting "it’s common sense to represent the society we serve."
"The promise of cellular therapy is solidifying in front of our eyes," Juno Therapeutics CEO Hans Bishop told investors and delegates. In an increasingly competitive field of CAR-T therapies, Bishop maintains that JCAR017 - Juno’s lead asset - has a potential best-in-class profile for the treatment of non-Hodgkin’s lymphoma; albeit if this argument may have weakened somewhat in light of new data presented at ASH in December - KOL Views Results: Leading oncologist says CAR-T therapies look more similar than different in DLBCL.
"Not all CAR-T cells are the same,” remarked Bishop in reference to the more precise CD4 and CD8 CAR-T cell dosing Juno has introduced with JCAR017. Superior tolerability should facilitate broader use in the outpatient setting, juno believes, with approximately 80 percent of NHL patients currently treated outside of an academic medical centre.
With outpatient data accumulating, showing a 40 percent reduction in hospital days among relevant patients, Juno appears confident use in this setting could occur at launch. "That is why we find our tolerability profile so encouraging, as it will allow us to move outside of those transplant centers and take JCAR017 to the site of care for many of these patients," said Bishop.
This advantage could, however, be eroded (at least partially) by a longer turnaround - or so-called ‘vein to vein’ time - of at least 21 days for Juno’s first-generation (i.e. JCAR017) product. Bishop suggested that a fourth generation CAR-T may reduce this turnaround time to between 3 and 6 days, which could also reduce associated costs by around 70 percent. At launch, however, Gilead has indicated it can manufacture the CAR-T cells for Yescarta at between 14 and 17 days.
Among the drug companies – especially those with biotech roots – with the most to gain from tax reform was Amgen, which trumpeted its hoard of overseas cash and strong desire to put it to use, while perhaps frustrating some investors with vague messaging about and when it would actually do so.
Amgen was not in shy about applauding the newly enacted tax reform in the US, as the company has $40 billion in overseas profits squirreled away to which – after paying a one-time repatriation tax of upwards of $6.5 billion – it will suddenly have unfettered access. What’s more, its corporate tax rate will be sliced to 21 percent from 35 percent.
Interestingly, Amgen does not appear averse to letting the money burn a hole in its pocket, as CFO David Meline said the newfound financial flexibility would not change the way the company is looking at business development.
“As a leading biologics manufacturer, our key priority is to seek to expand our portfolio of products that will bring improvements to standard of care. So that means continuing to invest in internal R&D efforts first and foremost,” he said, while also acknowledging that bringing in innovation – external products account for roughly 50 percent of revenues – has been and will continue to be a point of emphasis.
At the same time, when pressed during Amgen’s breakout session by questions about its M&A plans, management refused to be tied down as far as possible targets or timelines. CEO Robert Bradbury suggested the company is open to looking at early-, mid- or late-stage assets in all six of its therapeutic areas of interest, and noted that is not feeling any pressure to pull the trigger.
“There is a lot of competition [for deals] at moment and we are observing transactions at valuations above where we think we can earn an appropriate profit for shareholders right now,” said Bradbury, adding that "there is more capital chasing returns at the moment and we expect a shakeout – that is not to say, though, that we are waiting for a market downturn."
Excitement surrounding Nektar Therapeutics’ lead immuno-oncology (I/O) agent appeared palpable at JP Morgan 18 as investors, pleased by what they saw from data building on an encouraging mid-stage readout from November, pushed the company’s shares up almost 19 percent on January 9.
The Street is becoming increasingly confident that Nektar has hit on a winner with its NKTR-214, a pegylated interleukin-2 product that the company believes will emerge as an ideal complement for I/O drugs such as inhibitors of PD-(L)1 or IDO. (See ViewPoints: Nektar’s big splash in oncology could get a whole lot bigger.)
Last fall, Nektar reported that NKTR-214 plus Bristol-Myers Squibb’s Opdivo (nivolumab) achieved objective response rates of 63 percent in melanoma and 46 percent in renal cell carcinoma (RCC). This week, updated findings showed that all the unconfirmed responses have now not only been confirmed, but the response rate in RCC has actually increased to 57 percent.
Interestingly, NKTR-214 and Opdivo appeared to work about as well in patients regardless of PD-L1 status, which could give it a leg up on a combination like Opdivo plus Yervoy (ipilimumab) that has not fared as well in patients with low PD-L1 expression, not to mention the latter duo’s more problematic safety profile.
The breadth of NKTR-214’s potential will not have been lost on investors either, as the updated results showed the agent was active in five different tumours types, including bladder, non-small-cell lung and triple negative breast cancer.
All eyes will now turn to the American Society of Clinical Oncology (ASCO) meeting in June where dose-expansion data from PIVOT-02 should offer a better look at the durability of NKTR-214’s effectiveness.
Read our coverage of key news from day one of JP Morgan 2018 here