Inhibitor Therapeutics, Inc.

Current report

Itraconazole has demonstrated multiple antitumor mechanisms that provide a scientific rationale for its development in basal cell carcinoma (“BCC”). Investigators at Johns Hopkins University (“JHU”) identified itraconazole as an inhibitor of angiogenesis, demonstrating that it inhibits endothelial cell-cycle progression and blocks vascular endothelial growth factor (“VEGF”) and basic fibroblast growth factor (“bFGF”)-dependent formation of new blood vessels. Angiogenesis provides growing tumors with the vascular network required to deliver oxygen and nutrients. Human BCCs have been shown to possess an expanded microvascular bed compared with normal skin, including approximately 2.6-fold greater microvascular area, 2.0-fold greater microvessel length density and 3.9-fold greater red-cell flux. Accordingly, inhibition of angiogenesis may constrain the vascular support available to BCCs and contribute to itraconazole’s antitumor activity. Itraconazole has also demonstrated inhibition of Hedgehog signaling, a central driver of BCC tumorigenesis.

Current report

Itraconazole also exhibits substantial distribution into human skin. In a human pharmacokinetic study, skin tissue concentrations in the beard region and back were consistently higher than corresponding plasma concentrations after seven days of oral administration, while concentrations in sebum reached approximately ten times corresponding peak plasma concentrations. The study also demonstrated uptake of itraconazole by keratinocytes in the basal layer and prolonged persistence within keratinized skin tissues. We believe these distribution characteristics provide an additional pharmacologic rationale for investigating systemic itraconazole in cutaneous BCC.

Current report

In HP2001, no correlation was observed between serial trough plasma itraconazole concentrations and objective therapeutic response, and reductions in tumor measurements were not correlated with plasma itraconazole levels. Published human pharmacokinetic studies have shown that itraconazole distributes extensively into the skin following oral administration. Skin tissue concentrations can exceed corresponding plasma concentrations, itraconazole is taken up by keratinocytes in the basal layer of the epidermis, and concentrations in sebum have been reported at approximately ten times corresponding peak plasma concentrations. These findings provide a plausible explanation for why systemic plasma concentrations may not directly reflect drug exposure or activity at the cutaneous site of disease. The significance of this relationship has not been established, but it suggests that plasma concentrations alone may not be a reliable predictor of therapeutic response in BCCNS.

Current report

The primary efficacy endpoint we propose for this program is the rate and response of surgically eligible BCCs, meaning those tumors that have reached the anatomic site-referenced size at which surgical excision is warranted. This endpoint, which was the endpoint of the only randomized, placebo-controlled trial ever conducted in Gorlin syndrome, replaces the per-lesion response rate we had previously proposed to the FDA, and it is the basis on which we are seeking the Agency’s agreement that our existing clinical data may support a marketing application under Section 505(b)(2) of the Federal Food, Drug, and Cosmetic Act. See “Regulatory Developments and Proposed Development Pathway” below.

Current report

We engaged Avior Bio, Inc. (“Avior”) to develop novel oral formulations of itraconazole for our development program. As part of the formulation development program, Avior evaluated three itraconazole formulations in capsule format and assessed three prototype polymer compositions to create amorphous nano/microparticles using spray drying methods. The formulations were studied in a parallel group three-armed pre-clinical pharmacokinetic study in rats. The study included a formulation designed to mimic TOLSURA®, and two novel formulations developed to enhance itraconazole bioavailability. Each formulation was administered orally at an equivalent dose of 10 mg/kg. One of the novel formulations, AVF2-1, generated higher itraconazole plasma levels than the TOLSURA-mimicking formulation. Our provisional patent application covers the development of its amorphous nano/microparticle itraconazole formulations and the enhanced bioavailability observed in the rodent model. The claims are intended to protect the novel formulation and related methods of treatment informed by the efficacy results observed in the HP2001 study. In connection with any future New Drug Application (“NDA”), the Company intends to seek Orange Book listing of any issued formulation or composition patents that are eligible for listing.

Current report

Following the preclinical work, Avior completed further formulation development and manufactured two Inhibitor Therapeutics itraconazole capsules containing 65 mg and 75 mg of the selected itraconazole formulation. The purpose of selecting the specific dose strength was to demonstrate point estimate bio-similarities in Pharmacokinetic parameters to the observed HP2001 study. During 2026, we conducted a pilot, randomized, three-way crossover pharmacokinetic bioavailability study (ITZ101) in healthy adult subjects under fasting conditions comparing the two test formulations with TOLSURA® 65 mg as the reference product. Final study documentation was issued in July 2026.

Current report

The ITZ101 study demonstrated generally comparable pharmacokinetic profiles between the test formulations and the reference product, with the 75 mg formulation producing systemic exposure most comparable to TOLSURA. For the 75 mg formulation, the geometric mean ratios relative to TOLSURA for itraconazole AUC0-t and Cmax were 105.36% and 102.19%, respectively. The observed variability is consistent with the well-recognized pharmacokinetic characteristics of itraconazole, which has low aqueous solubility and historically variable oral absorption. Based on these results, we intend to advance a ~75 mg formulation in our development program. We expect the preclinical and human pharmacokinetic results generated through the Avior formulation development program to inform our ongoing regulatory strategy and discussions with the FDA regarding the development pathway for a potential NDA.

Current report

The pilot study described above is also intended to support the comparative bioavailability bridge between the itraconazole product used in our completed HP2001 study and our to-be-marketed formulation. We expect that such a bridge will be a required component of any marketing application submitted under Section 505(b)(2) of the Federal Food, Drug, and Cosmetic Act, which permits an applicant to rely in part on the FDA’s previous findings of safety and effectiveness for a previously approved drug.

Current report

Commercial and Economic Considerations

Current report

We have also prepared an internal illustrative analysis of the potential economic burden associated with the management of BCCs in patients with BCCNS. Because management of the disease currently relies heavily on repeated Mohs surgery, excisions, biopsies and other tumor-directed procedures, the cost of care can increase substantially as tumor burden increases. Using published literature, publicly available U.S. self-pay cost benchmarks and assumed utilization ranges, our analysis estimates monthly procedural costs of approximately $2,000 to $3,500 for a patient during periods of relatively low tumor burden, approximately $4,500 to $7,500 during periods of moderate tumor burden and approximately $7,500 to more than $14,500 during periods of high tumor burden. These estimates are illustrative and do not represent actual claims experience, contracted payer reimbursement rates or the expected cost of care for any particular patient. Actual utilization and costs may vary materially based on tumor number, anatomical location, treatment modality, insurance coverage and other factors.

Current report

We have separately developed an illustrative internal commercial model to evaluate the potential economic opportunity associated with an approved systemic therapy for BCCNS. The model assumes an estimated U.S. BCCNS population of approximately 11,000 patients, approximately one-third market penetration, and illustrative pricing of $4,000 to $5,000 per patient per month. Under those assumptions, approximately 3,700 treated patients would correspond to potential peak annual U.S. revenue of approximately $178 million to $222 million. The model also considers a commercialization ramp, potential orphan-drug exclusivity, a post-exclusivity erosion period and potential formulation patent protection over a 20-year modeled lifecycle. These analyses were prepared for internal strategic planning purposes, are highly sensitive to the assumptions used and should not be interpreted as Company financial guidance, a forecast of future revenues, an estimate of fair value or an indication that FDA approval or any particular level of pricing, reimbursement, market penetration or commercial performance will be achieved.

Current report

Regulatory Developments and Proposed Development Pathway

Current report

The most significant development in our program during 2026 has been a change in the primary efficacy endpoint we propose for the registration of itraconazole in BCCNS. We now propose the rate and response of surgically eligible basal cell carcinomas, meaning those tumors that have reached the anatomic site-referenced size at which surgical excision is warranted, in place of the per-lesion response rate we had previously proposed to the FDA. This was a primary endpoint of the randomized, placebo-controlled oral-vismodegib trial reported by Tang and colleagues in the New England Journal of Medicine in 2012 (the “Tang Trial”), in which the hedgehog pathway inhibitor vismodegib was compared with placebo. We believe this endpoint is the appropriate measure of benefit in this disease because it measures the surgical burden the disease imposes on patients, who are otherwise managed by repeated surgical excision over a lifetime, rather than the response of any individual lesion.

Current report

In the Tang Trial, the rate of new surgically eligible tumors fell from approximately 29 per patient-year on placebo to approximately 2 per patient-year on vismodegib, and the mean number of surgical excisions per patient fell from 4.4 to 0.31, with medians of 1.0 and 0 and P less than 0.001 for both outcomes. We regard the accompanying reduction in actual surgeries as important, because it indicates that the endpoint measures the morbidity the disease imposes rather than a surrogate for it. The Tang Trial enrolled a substantially higher-burden population than HP2001, as entry required at least 10 surgically eligible tumors at entry or during the preceding two years and the placebo arm had a baseline mean of approximately 37 such tumors, against a baseline mean of approximately 7 in HP2001. Because the rate at which new tumors appear scales with the number a patient already carries, the Tang rates are evidence that the endpoint responds to treatment and are not a benchmark for the population we intend to treat, and we do not present a direct comparison between the Tang rates and the HP2001 rates below.

Current report

The change in endpoint followed our interactions with the FDA during 2026. In February 2026, we submitted a meeting request and associated briefing materials to the FDA in support of our development program. On May 5, 2026, the FDA provided written responses in lieu of a meeting. In those responses, the FDA did not agree that a per-lesion response rate was an appropriate primary efficacy endpoint, questioned whether a reduction in the size of an individual basal cell carcinoma is by itself clinically meaningful in a patient who may have many such tumors, and recommended that we conduct a prospective, randomized, placebo-controlled trial. Following receipt of those responses we substantially repositioned our development strategy to respond to the Agency’s comments.

Current report

As supporting evidence for the proposed endpoint, we have applied the same site-referenced size thresholds to the target lesions that were already present at baseline in our completed HP2001 study. HP2001 was an open-label, single-arm study of itraconazole in 38 patients with BCCNS in which 477 target basal cell carcinomas were measured over the course of the study. Among the baseline target lesions meeting those thresholds, 53.4% met the criteria for an objective response, defined as a reduction of at least 30% in longest diameter; 86.9% were controlled, meaning they responded or remained stable; and the mean best reduction in longest diameter was approximately 41%. This analysis measures the response of tumors that were already present, which is a different measure from the rate at which new surgically eligible tumors arise. We present it as supporting evidence and do not combine the two measures.

Current report

We have also applied the same thresholds to the tumors that arose during HP2001. Ten new surgically eligible basal cell carcinomas were identified in 7 of the 38 patients, a rate of approximately 0.21 per patient-year over 46.7 patient-years of protocol follow-up. Measured over the 37.8 patient-years during which patients were actually receiving itraconazole, the corresponding rate is approximately 0.27 per patient-year. Under a narrower definition used in later development programs in this disease, which counts nose and periorbital tumors separately, the figures are 9 tumors in 6 patients and approximately 0.19 per patient-year. These are observed single-arm rates and are not treatment effects.

Current report

Because Gorlin syndrome requires management over a patient’s lifetime, we believe the ability of a patient to remain on therapy is a central component of the clinical utility of any chronic treatment. In the Tang trial, discontinuation of vismodegib for adverse events was 27%, or 7 of 26 patients, at a mean follow-up of approximately 8 months, and 54%, or 14 of 26 patients, by approximately 18 months, with only 1 of 5 eligible patients remaining on treatment at 18 months. In HP2001, treatment-related discontinuation of itraconazole for adverse events was 13%, or 5 of 38 patients, over a median of approximately 7 months of on-drug exposure. At approximately comparable duration the comparison is therefore 13% for itraconazole against 27% for vismodegib. These figures are drawn from different studies, are measured on different time bases because the Tang percentages are reported against observation time while the HP2001 percentage is reported against on-drug exposure, and are not the product of a head-to-head comparison. Neither vismodegib nor sonidegib is approved for the treatment of basal cell carcinomas in Gorlin syndrome; each is approved only for advanced or metastatic basal cell carcinoma, and use in patients with Gorlin syndrome is off-label.

Current report

On July 10, 2026, we submitted a meeting request and associated briefing package to the FDA to discuss the clinical development of itraconazole for the treatment of surgically eligible basal cell carcinomas in patients with BCCNS. On July 23, 2026, the FDA granted the meeting request, classified the meeting as a Type C meeting, and determined that written responses would be the most appropriate means of responding to our questions, with the result that a meeting will not be scheduled. The FDA acknowledged receipt of our briefing package and stated that its goal date for providing written responses is by the end of September 2026. The FDA also noted that if it determines the materials in our briefing package are inadequate, it may cancel or reschedule the agreement to provide written responses, in which case a new meeting request would be required. Our briefing package sets out the proposed endpoint, the supporting analyses of the HP2001 data, our responses to the FDA’s May 5, 2026 comments, and the questions on which we are seeking the Agency’s guidance, including whether the existing data are adequate to support a marketing application under Section 505(b)(2).

Current report

The analyses described above are descriptive characterizations of measurements collected prospectively in a single-arm, open-label study. They are not the results of a controlled, hypothesis-testing comparison against a concurrent control, they have not been reviewed or accepted by the FDA, and they may not be predictive of the results of any future controlled study. There can be no assurance that the FDA’s written responses will be favorable, that they will be provided by the stated goal date, or that the FDA will agree with our proposed endpoint, our characterization of these analyses or our proposed regulatory pathway. If the FDA does not agree, we may be required to conduct one or more additional clinical trials before a marketing application could be submitted or approved, which would require substantial additional capital and would materially delay any potential commercialization. See Item 1A, “Risk Factors.”

Current report

For the six months ended June 30, 2026 compared to the six months ended June 30, 2025

Previous report

We have engaged Avior Bio, Inc. (“Avior”), to develop a novel formulation of itraconazole. Avior has completed the formulation development process, and upon finalization, will conduct a pharmacokinetic (“PK”) crossover study of the generic formulation and the formulation that was used within the HP2001 study in preparation for a new pre-IND and New Drug Application (“NDA”). As all formulations consist of the same active pharmaceutical ingredients (“API”), we expect that our new, novel formulation to exhibit pharmacological properties extremely similar to those of the formulation used in the HP2001 clinical study.

Current report — wording carried from elsewhere

Research and Development Expenses. We incurred $0.2 million and $0.3 million of research and development expenses during the three months ended June 30, 2026 and June 30, 2025, respectively. The expenses are primarily internal personnel costs, consisting of salaries, benefits and other related costs, as well as amounts paid to third parties to support our research and development activities. The decrease was primarily the result of a decline in third party research and development costs due to the progress of the work performed relating to our contractual arrangement with Avior. We expect research and development expenses to increase in the future, depending on the results from our regulatory interactions with the FDA.

Current report — wording carried from elsewhere

General and Administrative Expenses. We incurred approximately $0.8 million in general and administrative expenses during each of the six months ended June 30, 2026 and June 30, 2025. During each of the six months ended June 30, 2026 and 2025, general and administrative expenses were comprised primarily of compensation costs of $0.4 million, professional services fees of $0.2 million, and insurance costs of $0.2 million.

Current report — wording carried from elsewhere

Interest income. We earned $0.01 million and $0.08 million of interest income during the six months ended June 30, 2026 and June 30, 2025, respectively. The interest income is generated from deposits held in our depository accounts and the decrease is the result of less deposits within our money market account during the current period.