My summary of Nektar’s conference call. It was rather amazing (to me anyway). Here it is:
Our submission of an NDA for NKTR-181 will occur this month.
NKTR-214 is entering Phase 3 trials and
NKTR-262 is being evaluated in the recently initiated REVEAL study,
NKTR-358 is progressing with our immunology program
In immuno-oncology (IO), we remain focused on developing a full pipeline of new medicines that address the key components of the immune cycle, in order to restore immune surveillance and properly harness the body’s immune system to fight cancer.
Our new BMS collaboration provides a platform of us to develop our lead IO candidate NKTR-214 broadly and rapidly, with over 20 registrational trials in nine tumor types. We believe this will allow us to achieve our goal of establishing NKTR-214 as a backbone of cancer care across multiple indications.
In immunology, we have now advanced NKTR-358 into patients with the initiation of the Phase 1b multiple ascending dose trail being conducted in lupus patients.
Because of NKTR-181’s significant potential, and our current financial strength, our focus is no longer a near-term economics for NKTR-181, but rather to retain as much back-end value as possible. As such, we are evaluating several strategic structural alternatives for the commercialization of NKTR-181. (They had planned to mostly sell N-181 for cash, but they will now keep N-181 or partner it instead of selling it to raise cash, which they no longer need! )
We may establish a separate majority-owned subsidiary, with one or more partners to launch this important molecule. This is consistent with our desire to focus our resources on our immuno-oncology and immunology pipeline, while maximizing the value of N-181 for our shareholders.
N-214:
Collaboration with Bristol Meyers: We have already begun planning the next steps in the joint development program with BM. The intent of this program is to advance this potential combination regimen in IO to as many patients as possible as quickly as possible.
Thus, we are planning to start our first Phase 3 trials for N-214 with Opdivo in the third quarter of this year. The first two trials will be in first line melanoma and first line renal cell carcinoma. In the second half of 2018, we’ll also design and launch our first registrational trials in lung cancer. We are highly focused on a multi-pronged approach for N-214 plus Opdivo in lung cancer, which envisions multiple registrational trials in different patient populations. Under the framework of this new collaboration, we are planning over 20 registrational enabling trials with BM, that will enroll about 15,000 patients in nine tumor types.
Collaboration with Takeda: We just initiated a new clinical collaboration with Takeda, which includes a Phase 1 study evaluating the combination of NKTR-214 with TAK-659 in patients with non-Hodgkin’s lymphoma. It will start in the second half of this year. We are extremely excited about the possibilities of evaluating N-214 for the first time in a liquid tumor setting.
Financial Status: After the signing of Bristol-Myers collaboration, we are in an exceptionally strong financial position, which allows us to execute on our vision for our portfolio in immuno-oncology. Our pipeline of IO candidates beyond N-214 includes N-262, a TLR-78 agonist and N-255, an IO-15 candidate, which can stimulate both NK cells and memory T-cells.
We ended the first quarter with cash of $334 million, but this did not include the payments from Bristol-Myers Squibb for the strategic collaboration that closed on April 3rd.
At the closing, we received $1.85 billion from BMS, comprised of a $1 billion upfront payment and an $850 million premium equity investment. We still expect to end the year with a cash position of approximately $1.9 billion to $1.925 billion.
Reveal Trial: In April, we dosed the first patient in the REVEAL trial, evaluating a combination of N-262 with N-214. The trial is enrolling up to 400 patients with eight different tumor types.
The first stage will assess the doublet of N-262 and N-214. Following that, the second stage will have the option to evaluate NKTR-262 and NKTR-214 plus Opdivo. We expect to have initial early data sometime in the fourth quarter of this year.
N-262 targets the innate immune system and N-214 targets the adopted immune system. This combination thus engages the same biological pathways that our immune system uses to fight infections.
Except in this case, we use the frequent injection of NKTR-262 into one or two tumor legions to educate the immune system. And NKTR-214 to expand and propagate the educated immune system response throughout the entire body to target all tumor lesions even one is not injected with NKTR-262. We call this an abscopal immune response and we routinely see this in preclinical tumor models using NKTR-262 and NKTR-214.
Propel Study: The PROPEL study is not a partnership and is fully run and sponsored by Nektar. We are enrolling patients who have bladder cancer or non-small cell lung cancer with N-214 plus atezolizumab and those patients are patients.
In addition we are combining N-214 plus pembrolizumab in patients who have melanoma, in patients who have non-small cell lung cancer, who have PD-L1 greater than 50%, or small cell lung cancer patients, or again bladder cancer patients. We are actively enrolling those patients. In the second half of this year we will have data to share.
Immunology: Now an update on N-358 in our Eli Lilly collabration. The initial data from our ongoing first-in-human Phase 1 trial of N-358 in healthy volunteers has shown dose-dependent increases in T regulatory cell levels with no increase in conventional T-cells or NK cells. This is comparable to what we saw in our non-human primate models and we are extremely pleased that this mechanism has now been confirmed in humans.
We have now dosed our first patient in the Phase 1b multiple ascending dose trial in patients with lupus. This continues to advance quickly and we expect initial data sometime in the second half of next year. We are very excited about the potential of N-358 as a resolution therapeutic (cure?) to bring a new paradigm to the treatment of autoimmune disease and chronic inflammatory indications.
As you know, Nektar is responsible for all activities up to the end of Phase 1 and then Lilly will take the lead from Phase 2 onwards.
Tying it up: In all cases, we believe to have a strong scientific rationale for the combination that is both specific to the individual combination partners and the tumor selection for the intended use of each combination.
My Conclusion (Saul) – In my end of the month summary I said that I wouldn’t add to my Nektar position any further, but after reading this amazing summary I couldn’t help myself, and went out and bought some more.
But that’s just what I did. You should make your own decision.
Best,
Saul