Bolt Biotherapeutics Inc Aktie

Good morning, and welcome to the Bolt Biotherapeutics Conference Call and Webcast. Please note that this call is being recorded and will be available for replay on boltbio.com. [Operator Instructions] I will now turn the call over to Willie Quinn, President and Chief Executive Officer of Bolt Biotherapeutics. Sir, please go ahead.

Thank you, and good morning. Before we begin, I'd like to direct you to the forward-looking statements on Slide 2. Our remarks today will include forward-looking statements including statements concerning the transaction, financing, anticipated clinical development and future milestones that are subject to risks and uncertainties described in Bolt's SEC filings and in our press release and presentation. The press release and this presentation are available on the Investor Relations section of Bolt's website.

We'll start with an overview of the transaction on Slide 3. Last Friday, October 23, Bolt announced that it has acquired Prana Therapies in a sign-and-close, stock-for-stock reverse merger and entered into an agreement for a concurrent private placement financing of $120 million in upfront proceeds and up to an additional $60 million in gross proceeds upon exercise of accompanying warrants. Following the transaction, Prana's pipeline is expected to become the primary development focus of the company. The financing is expected to support the advancement of Prana's clinical stage programs through multiple important milestones, including Phase II proof-of-concept data for PRA-216 expected in 2027.

Subject to stockholder approval, the non-voting convertible preferred stock issued in connection with the transaction and financing is expected to convert into Bolt common stock following the planned stockholder vote. In connection with the transaction, Dr. Sheila Gujrathi, Co-Founder and Chief Executive Officer of Prana Therapies, has been appointed Chief Strategy Officer of Bolt and has joined the Bolt Board of Directors. We are pleased to welcome Sheila and the broader Prana team and believe the combination creates a compelling path forward for Bolt and its stockholders.

With that, I'll turn the call over to Sheila to introduce Prana's programs and the opportunity ahead for the company.

Thank you, Willie, and thank you to everyone joining us this morning. Starting on Slide 4. This transaction and financing provide the capital and public company foundation to advance the programs we built at Prana through a very data-rich period ahead. The $120 million in upfront gross proceeds from the private placement is expected to fund operations into 2028, which we expect to take us through multiple clinical and preclinical milestones.

The company will be focused on advancing Prana's pipeline of next-generation half-life-extended multispecific antibodies led by PRA-216, which is in Phase II development for multiple high-value inflammatory indications, including asthma, chronic obstructive pulmonary disease or COPD, and atopic dermatitis or eczema, with an additional Phase II study planned in eosinophilic esophagitis or EoE. Over the next few minutes, I'll introduce Prana's programs, the homegrown INSPIRE multispecific antibody platform behind these programs, and the exciting clinical and preclinical milestones that lie ahead for our programs and discovery pipeline.

Moving to Slide 5. We are building a new generation of half-life extended multispecific antibodies with our INSPIRE platform, designed to deliver potentially best-in-disease therapies initially focused on immunology and inflammation. We built the INSPIRE platform at Prana to solve for the whole product profile. Our key focus is on improving clinical outcomes by combining the right complementary clinically validated targets to overcome monotherapy efficacy ceilings.

In addition to better efficacy, we understand the need to deliver convenient, patient-friendly medicines. The INSPIRE platform was designed for exposure and target coverage to enable durable efficacy for chronic diseases with infrequent at-home dosing with an auto-injector. In designing INSPIRE, we tasked ourselves with solving the additional challenges encountered by other bispecific formats. The INSPIRE platform was built on a fully-human IgG-based architecture, which has enabled meaningful improvements in stability, manufacturability, high-concentration subcutaneous formulation and decreased immunogenicity risk. Our lead program has now provided clinical validation of our platform, and we continue to generate new wholly-owned programs and expand our INSPIRE pipeline into additional indications.

On Slide 6 now. Complementing the thesis and strategy I just outlined is a team with deep experience and expertise across complex biologics drug discovery and immunology drug development. My background spans immunology development and company building, including Genentech, Bristol-Myers Squibb, Receptos and Gossamer Bio. Ryan Sullivan, Prana's Chief Scientific Officer, brings extensive experience in complex biologics discovery and early development. Hector Ortega, Prana's Chief Medical Officer, has led development programs across several of the mechanisms central to type 2 inflammatory disease. Tina Trout leads corporate development and brings both large pharma and biotech transaction experience. Miguel Sanjuan, Prana's Co-Founder and Strategic Scientific Adviser, has spent more than 25 years developing biologics, including work on half-life extension technology. Together, we believe this team is well equipped to efficiently execute on our clinical development programs and propel our exciting discovery platform.

On Slide 7, I'll provide an overview of our programs. PRA-216 is our lead program and our first clinical validation for the platform. PRA-216 targets IL-4Ra and TSLP and is now in Phase II development in asthma, COPD and atopic dermatitis with an EoE study planned. Patient proof-of-concept data across all 4 studies are expected beginning in the second quarter of 2027. Our second program is an IL-31 containing bispecific being developed initially for atopic dermatitis. We expect to move that program into the clinic and generate initial clinical data in the second half of 2027. Behind those programs, the INSPIRE platform continues to generate additional wholly-owned candidates, with programs 3 and 4 expected to advance through IND-enabling development in the second half of 2027. We are excited for a potentially catalyst-rich 2027 and beyond.

Turning to Slide 8. We are developing PRA-216 for large clinically validated markets where biologics have already changed the standard of care, yet where substantial unmet need remains. Asthma, COPD, and atopic dermatitis, each represent large global markets with hundreds of millions of patients worldwide. Importantly, these are also markets where validated biologics have established the value of targeting type 2 inflammation, but there is still substantial room to improve outcomes. As shown here on the right, even highly effective monotherapies leave meaningful room for improvement in reducing asthma and COPD exacerbation rate. Similar unmet need exists in additional indications. That is the opportunity PRA-216 is designed to address, moving beyond the efficacy ceiling of a single mechanism by combining 2 of the most clinically validated targets in atopic and inflammatory diseases, TSLP and IL-4Ra.

Turning to Slide 9. The target combination essential to the PRA-216 profile. IL-4Ra block signaling from both IL-4 and IL-13, giving us broad downstream type 2 pathway coverage. We've deliberately chosen to target IL-4Ra rather than IL-13 alone, because we believe that inhibiting both IL-4 and IL-13 signaling is critical to fully realizing the therapeutic potential of this biology, particularly in respiratory diseases. However, effective targeting of IL-4Ra requires an architecture optimized for durable exposure. Our INSPIRE platform is designed for exactly that, enabling us to pursue this approach without compromising exposure or durability. And as you'll see from our clinical data, we believe we've been able to deliver on that promise.

TSLP is complementary to IL-4Ra. It sits upstream at the epithelial interface and influences multiple inflammatory pathways with the potential to broaden activity across heterogeneous patient population. Together, targeting these pathways provides both upstream and downstream inhibition of type 2 inflammation. Our optimized target product profile is the following: first, the potential for deeper and more durable efficacy by combining these complementary mechanisms. Second, broader disease coverage, including heterogeneous type 2 patient populations and the significant proportion of patients living with multiple type 2 inflammatory conditions, where PRA-216 has the potential to treat not just a patient's primary disease, but also their comorbid atopic conditions. And third, a convenient maintenance profile, potentially offering patients in every 8- to 12-week dosing regimen with a convenient single at-home auto-injector.

Ryan will now take you through how we designed PRA-216 to achieve this intended profile and the Phase I data we have generated to date.

Thanks, Sheila. Moving to Slide 10 now. Here we show how we think about differentiation for PRA-216. For a multispecific and chronic inflammatory disease, we believe you need to deliver both the right biology and sustained exposure. Either one in isolation is insufficient. PRA-216 combines IL-4Ra and TSLP blockade to provide that broad inflammatory pathway suppression, and INSPIRE is designed to enable that sustained exposure and target coverage over an extended maintenance interval. That combination is what we are aiming to achieve, a differentiated biology, durable exposure and a practical subcutaneous product profile, with Phase II trials now evaluating every 8-week maintenance dosing with the potential to evaluate every 12-week dosing in future trials.

On Slide 11 now. The preclinical work here demonstrates part of the data set that helped us select the INSPIRE format. We evaluated several bispecific architectures using the same binders and the same YTE modified Fc, which allowed us to look at the contribution of format itself. In nonhuman primates, the INSPIRE construct showed a substantially longer half-life than the comparator bispecific formats, which included alternative formats like SCFE fusions, all evaluated in the same study. Those findings informed an important design principle for us.

Improved FcRn binding via YTE is necessary but not sufficient for durable half-life extension in a bispecific. The underlying architecture is also a critical factor for realizing extended exposure in vivo. We believe INSPIRE is a scaffold that is sufficiently stable to deliver that robust in vivo half-life extension, and the clinical data we will show next are consistent with the extended exposure profile we observed preclinically.

I'll now turn it over to Hector to discuss our Phase I study design and safety profile.

Thanks, Ryan. On Slide 12 now. Our Phase I study enrolled 57 healthy volunteers in a randomized, double-blind, placebo-controlled, single- and multiple-ascending dose design. We evaluated both intravenous and subcutaneous administration across a range of doses. In the multiple-dose cohort, participants received 3 doses at weeks 0, 2 and 4, which established the induction regimen we are now using in Phase II. PRA-216 was well tolerated. As of the September 1 data cut-off shown here, there were no serious adverse events or adverse events of special interest, no grade 3 or greater treatment-emergent adverse events, no injection site reactions or local pain, and no conjunctivitis. This safety profile supported our decision to advance rapidly into Phase II.

I will turn it back to Ryan now.

Thanks, Hector. Moving to Slide 13 now. The pharmacokinetic results were a particularly important part of the Phase I study. Following a single intravenous dose, we observed over 16 weeks of exposure. With a single subcutaneous dose, PRA-216 demonstrated 85% bioavailability. And following the 3-dose subcutaneous induction regimen, exposure extended beyond 20 weeks.

We also observed very low immunogenicity. Only a single subject of the 43 PRA-216-treated participants developed a low-titer antidrug antibody response, representing a 2.3% total incidence across the study, in line with the human IgG-based design of the INSPIRE platform. These data showed sustained exposure following subcutaneous administration and support the every 8-week maintenance regimen now being evaluated in Phase II.

Moving to Slide 14. Using those Phase I PK data, we modeled the planned clinical dosing regimen for our Phase II trials. Our simulations support a 600-milligram dose every 8 weeks during maintenance with modeled exposure remaining above our target thresholds for both mechanisms. Importantly, the model is intentionally conservative. It treats each pathway independently and assumes no additional pharmacologic benefit from simultaneously inhibiting IL-4Ra and TSLP. Our Phase II study is evaluating this every 8-week regimen. As we generate patient PK, PD and efficacy data, we expect to be able to characterize the contribution of the dual target biology more fully and determine whether longer maintenance intervals may be appropriate to evaluate in the future.

On Slide 15 now. We also saw clear and durable pharmacodynamic activity at the 600-milligram multiple dose regimen. Serum TARC, a marker of IL-4 and IL-13 signaling, declined by a median of approximately 50% through week 12. Blood eosinophils declined rapidly and remained suppressed through week 12, consistent with activity on the TSLP pathway. And serum IgE declined by approximately 25%, consistent with sustained suppression of type 2 inflammatory signaling. These biomarker data are consistent with engagement of both components of PRA-216 and showed durable pharmacodynamic activity through at least the end of the first maintenance interval.

Notably, this healthy volunteer data broadly compares very favorably with available monotherapy data and other bispecific assets in development. As we move further into patient populations, we expect the depth of activity to potentially increase further, and we look forward to seeing that potential translate into meaningful clinical benefits in our upcoming Phase II readouts.

And with that, I will turn it back to Sheila.

Thanks, Ryan. Now on Slide 16. To summarize the Phase I program, PRA-216 met or exceeded the objectives we set for the study. We established a favorable safety and tolerability profile in healthy volunteers. We demonstrated sustained exposure, strong subcutaneous bioavailability and very low observed immunogenicity. And we saw rapid and durable pharmacodynamic activity across multiple type 2 biomarkers. These findings support the optimized product profile we designed PRA-216 to achieve. And we have moved quickly into Phase II studies in asthma, COPD and atopic dermatitis, with a study in EoE being planned.

Importantly, we believe these are robust, adequately sized studies designed to evaluate key clinical and pharmacodynamic endpoints with longer-term follow-up to assess durability of response and inform the potential for less frequent dosing. We expect data readouts on all 4 programs beginning in the second quarter of 2027 and continuing through the fourth quarter. These studies are designed to inform our Phase III trial design, and Phase III enabling activities are already progressing in parallel, positioning PRA-216 to move efficiently into pivotal trials in early 2028.

On Slide 17. Looking ahead, we believe the company is well positioned for an exciting period of growth and value creation with a potentially best-in-disease lead program, a differentiated multispecific antibody platform, and a strong balance sheet to advance our clinical development strategy and broader pipeline. With multiple important catalysts expected over the next 12 to 18 months, we look forward to demonstrating the potential of PRA-216 while further validating our INSPIRE platform and its potential to enable a new generation of differentiated therapies.

Thank you to the Bolt team and our investors for their support, and thank you all for joining us this morning. I'll turn the call back to the operator.

That concludes today's call. Thank you for joining, and you may now disconnect. Everyone, have a great day.