Bolt Biotherapeutics, Inc. Common StockBOLT
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Bolt Biotherapeutics, Inc. Common Stock M&A announcement

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Operator

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. All participants are in a listen-only mode. I will now turn the call over to Willie Quinn, President and Chief Executive Officer of Bolt Biotherapeutics.

Willie QuinnPresident and CEO

Sir, please go ahead. Thank you, and good morning.

Willie QuinnPresident and CEO

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.

Willie QuinnPresident and CEO

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.

Sheila GujrathiChief Strategy Officer

Thank you, Willy, 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 pre-clinical 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.

Sheila GujrathiChief Strategy Officer

Over the next few minutes, I will 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.

Sheila GujrathiChief Strategy Officer

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 have 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.

Sheila GujrathiChief Strategy Officer

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 Advisor, 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 will provide an overview of our programs. PRA-216 is our lead program and our first clinical validation for the platform. PRA-216 targets IL-4 receptor alpha 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 four studies are expected beginning in the second quarter of 2027.

Sheila GujrathiChief Strategy Officer

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.

Sheila GujrathiChief Strategy Officer

As shown here on the right, even highly effective monotherapies leave meaningful room for improvement in reducing asthma and COPD exacerbation rates. 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 two of the most clinically validated targets in atopic and inflammatory diseases, TSLP and IL-4 receptor alpha. Turning to slide 9. The target combination is central to the PRA-216 profile. IL-4 receptor alpha blocks signaling from both IL-4 one, IL-4, and IL-13, giving us broad downstream type 2 pathway coverage. We have deliberately chosen to target IL-4 receptor alpha 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-4 receptor alpha requires an architecture optimized for durable exposure.

Sheila GujrathiChief Strategy Officer

Our INSPIRE platform was designed for exactly that, enabling us to pursue this approach without compromising exposure or durability. As you will see from our clinical data, we believe we have been able to deliver on that promise. TSLP is complementary to IL-4 receptor alpha. It sits upstream at the epithelial interface and influences multiple inflammatory pathways with the potential to broaden activity across heterogeneous patient populations. 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.

Sheila GujrathiChief Strategy Officer

Third, a convenient maintenance profile, potentially offering patients an 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.

Ryan SullivanChief Scientific Officer

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-4 receptor alpha 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. 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 dataset that helped us select the INSPIRE format.

Ryan SullivanChief Scientific Officer

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 non-human primates, the INSPIRE construct showed a substantially longer half-life than the comparator bispecific formats, which included alternative formats like scFv 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 will now turn it over to Hector to discuss our phase I study design and safety profile.

Hector OrtegaChief Medical Officer

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 three doses at weeks zero, 2, and 4, which established the induction regimen we are now using in phase II. PRA-216 was well-tolerated. As of the September 1st 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.

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