Innate Pharma, the French biotech darling known for its innovative forays into immunotherapy, just held its Q1 2024 earnings call. While analysts focused on the upcoming ASCO data for lacutamab and the progress of their ANKET platform, something else caught my eye: a subtle but potentially game-changing shift in Innate's strategy.

Buried within the discussion about lacutamab's development in Peripheral T-cell Lymphoma (PTCL) is a telling admission. Innate has decided not to reopen recruitment for the Phase 1 monotherapy trial. Why? Because the number of observed objective responses did not meet their pre-specified threshold.

On the surface, this seems like a simple setback. But dig deeper, and you'll find Innate is not just chasing response rates; they're prioritizing *tolerability*.

Sonia Quaratino, Innate's Chief Medical Officer, plainly states that the PTCL space is crowded with therapeutic options that "provide quite a robust number of objective responses." Their internal bar was "quite high" because they weren't solely focused on matching existing therapies in terms of tumor shrinkage.

The key takeaway? Innate seems to be recognizing that in a crowded therapeutic landscape, tolerability and a favorable safety profile can be just as crucial as raw efficacy, particularly in patient populations with complex comorbidities.

This focus on tolerability is further underscored by Quaratino's comments about lacutamab's potential in PTCL combination therapy with chemotherapy (GEMOX). She highlights the drug's "extremely good safety profile" as a significant advantage compared to other treatments with "harsher" profiles, particularly for patients who can't handle more aggressive therapies.

Innate's emphasis on tolerability isn't just a PTCL phenomenon. It seems to be woven into their broader strategy, particularly with their ANKET platform and emerging ADC portfolio.

With IPH6501, their second-generation ANKET targeting CD20, Sonia Quaratino explicitly calls out its disruptive mechanism of action and emphasizes its off-the-shelf nature and lack of lymphodepletion requirements compared to CAR-T and other cell therapies. These characteristics, coupled with the anticipated bystander effect eliminating both CD20 positive and negative tumor cells, suggest Innate is again aiming for a treatment that combines potent efficacy with a manageable safety profile.

This focus on creating tolerable, potentially best-in-class treatments becomes even more pronounced when examining their ADC strategy. With IPH45, their Nectin-4 targeting ADC, Innate specifically chose a payload with a strong bystander effect to address tumor heterogeneity and potential resistance mechanisms.

Preclinical data presented at AACR showcased IPH45's efficacy in models refractory to PADCEV, the current standard of care Nectin-4 ADC. But what's particularly noteworthy is the potential for IPH45 to demonstrate efficacy in tumors with low or heterogeneous Nectin-4 expression, a segment where PADCEV struggles.

This could signify a move towards expanding the treatable patient population while maintaining a manageable safety profile, effectively carving out a unique niche for Innate's ADC.

The Hypothesis: Is a "Tolerability Premium" Emerging?

Innate's strategic shift could be a harbinger of a broader trend within oncology drug development. As the therapeutic landscape becomes increasingly crowded, and the focus on personalized medicine intensifies, could a "tolerability premium" be emerging?

Imagine a scenario where two therapies demonstrate similar efficacy, but one has a significantly better safety profile and is easier to administer. Which treatment will physicians, patients, and payers gravitate towards?

It's not a stretch to imagine that the more tolerable option, even if priced at a premium, could become the preferred choice.

Innate Pharma, with its emphasis on combining efficacy and tolerability, might be positioning itself at the forefront of this potential paradigm shift. They're not just developing new drugs; they're crafting a future where cancer treatment isn't synonymous with debilitating side effects, paving the way for a new era of effective and *tolerable* therapies.

The Numbers:

To substantiate this hypothesis, let's look at some numbers. While specific response rates for PTCL haven't been disclosed, Innate's decision to halt monotherapy recruitment suggests they were below those of current standard-of-care treatments, which can range from 40% to 70% ORR depending on the specific PTCL subtype.

However, the tolerability profile of lacutamab in CTCL, with a 87.5% clinical benefit rate and median PFS of 8 months in heavily pre-treated Sezary syndrome patients, suggests a favorable safety profile that could translate to PTCL combination therapy.

Furthermore, Innate's cash runway through the end of 2025, despite not factoring in potential milestones from existing partnerships or new agreements, indicates a solid financial position that allows them to prioritize long-term strategic goals over short-term gains.

Innate Pharma Pipeline

Reference: Innate Pharma Pipeline

Clinical Trial Progress: Lacutamab vs. IPH6501

Reference: Q1 2024 Earnings Call Transcript

Innate's strategic shift might be subtle, but it's potentially profound. They are betting on a future where tolerability becomes a core driver of value in cancer treatment. Whether this hypothesis proves true remains to be seen, but Innate Pharma is certainly a company to watch as the oncology landscape continues to evolve.

"Fun Fact: NK cells, the key players in Innate Pharma's ANKET platform, were initially discovered in the 1970s due to their unique ability to kill tumor cells without prior sensitization. This "natural born killer" ability makes them a powerful weapon in the fight against cancer."