Clinical Development - STAR-0215 is in clinical development for hereditary angioedema (HAE) and aims to be a best-in-class treatment with potential administration every three or six months[56] - The Phase 1a clinical trial for STAR-0215 showed it was well-tolerated across all dose levels, with an estimated half-life of up to 117 days and sustained target engagement for at least three months[56] - The company initiated a Phase 1b/2 trial called ALPHA-STAR in February 2023, evaluating safety and quality of life in HAE patients[56] - Initial results from the Phase 1a trial are expected in the fourth quarter of 2023, with final results also anticipated in the same timeframe[56] Financial Performance - Research and development expenses decreased by 22% to $8.0 million for the three months ended March 31, 2023, down from $10.4 million in the same period in 2022[64] - The company reported an accumulated deficit of $518.8 million as of March 31, 2023, with losses from operations of $13.5 million for the three months ended March 31, 2023[59] - General and administrative expenses increased by 9% to $5.5 million for the three months ended March 31, 2023, compared to $5.0 million in the same period in 2022[64] - Total operating expenses decreased by $1.885 million to $13.493 million for the three months ended March 31, 2023, compared to $15.378 million in the same period of 2022[66] - Net loss narrowed by $4.135 million to $11.188 million for the three months ended March 31, 2023, compared to a net loss of $15.323 million in the same period of 2022[66] - Other income increased significantly to $2.305 million for the three months ended March 31, 2023, from $55 thousand in the same period of 2022, primarily due to higher yields on interest-earning assets[67] Cash and Funding - Cash, cash equivalents, and short-term investments totaled $213.3 million as of March 31, 2023, expected to fund operations through the first half of 2025[59] - The company raised an aggregate of $579.3 million through equity financings since inception, including a public offering that closed on December 19, 2022, generating net proceeds of $107.6 million[70] - Net cash used in operating activities was $13.253 million for the three months ended March 31, 2023, compared to $12.559 million in the same period of 2022[74] - Net cash provided by investing activities was $194.992 million for the three months ended March 31, 2023, primarily from maturities of short-term investments[74] - The company anticipates needing substantial additional funding to complete the development and commercialization of STAR-0215 and other product candidates[69] - The company has no committed external sources of funds and may need to seek additional financing sooner than planned due to various risks and uncertainties[69] Corporate Governance - The 2022 Inducement Stock Incentive Plan has been amended and incorporated by reference in the current report[10.1] - The principal executive officer and principal financial officer have certified compliance with the Securities Exchange Act of 1934[31.1][31.2] - The report includes certifications pursuant to the Sarbanes-Oxley Act of 2002[32.1] - Inline XBRL Instance Document is included, with embedded XBRL tags[101.INS] - The report is signed by Noah C. Clauser, Chief Financial Officer, on May 11, 2023[83]

Financial Data and Key Metrics Changes - The company reported a net loss of $13.3 million for Q4 2022, translating to $0.72 per share, and a full-year net loss of $51.8 million or $3.55 per share [29] - Cash, cash equivalents, and short-term investments increased to $226.4 million as of December 31, 2022, compared to $116.6 million as of September 30, 2022, providing a cash runway through the first half of 2025 [28][29] Business Line Data and Key Metrics Changes - The STAR-0215 program is progressing with positive results from the Phase 1a clinical trial, and the Phase 1b/2 ALPHA-STAR trial is currently underway [8][32] - The company aims for STAR-0215 to become the first-choice preventative treatment for HAE, with administration every 3 or 6 months [6][8] Market Data and Key Metrics Changes - The global HAE treatment market was over $2 billion in 2022 and is projected to grow to $4.2 billion by 2028, driven by earlier diagnoses and increased treatment options [10] - A recent market research study indicated that 100% of surveyed HAE patients expressed willingness to try a product like STAR-0215, with nearly 70% being very willing to switch to it [11][39] Company Strategy and Development Direction - The company is focused on transforming the HAE treatment paradigm with STAR-0215, which is designed for long-acting administration and aims to reduce treatment burden for patients [6][8] - The ALPHA-STAR trial is designed to assess the long-term effectiveness of STAR-0215 in preventing HAE attacks, with initial proof-of-concept results expected in mid-2024 [23][32] Management's Comments on Operating Environment and Future Outlook - Management expressed optimism about the potential of STAR-0215 to provide long-acting effective attack prevention for HAE patients, emphasizing the importance of patient feedback in guiding development [30][32] - The company is well-funded to achieve its goals, with a strong cash position supporting its operational plans through 2025 [28][32] Other Important Information - The company is exploring a 6-month dosing interval for STAR-0215, with initial results from additional cohorts expected in Q4 2023 [7][30] - The ALPHA-STAR trial is expected to include a new cohort to assess the effects of a subcutaneous dosing regimen targeting high initial concentrations of STAR-0215 [24][32] Q&A Session Summary Question: Concerns about YTE modifications and long-term side effects - Management indicated that no specific safety issues have been reported with YTE modifications in other antibodies studied, providing reassurance for STAR-0215 [36] Question: Market dynamics and competition in the HAE space - The company acknowledged the growing preventative market and expressed confidence in STAR-0215's profile to transition patients from existing treatments [39] Question: Financial outlook and operational expenses - Management provided guidance that current cash supports operations through the first half of 2025, with a gradual ramp in expenses expected as clinical activities increase [41] Question: Impact of Phase 1 study data on future development - The data from the ongoing Phase 1 study is expected to inform the strategy for STAR-0215's clinical development, particularly regarding dosing regimens [44] Question: Design considerations for the ALPHA-STAR trial - The trial was designed to eliminate the placebo group to enhance patient comfort and participation, with a focus on robust data collection [50] Question: Expected proof-of-concept data timeline - Initial proof-of-concept data from the ALPHA-STAR trial is anticipated in mid-2024, with a focus on demonstrating meaningful reductions in HAE attacks [52]

Q4/FY 2022 Financial Results and Business Update March 22, 2023 Confidential 1 Forward Looking Statements Thispresentationandvariousremarkswemakeduringthispresentationcontainforward-lookingstatementswithinthemeaningofapplicablesecuritieslawsandregulationsincluding,butnotlimitedto,statements regarding: expectationsregardingthepotentialsignificanceofthepreliminaryandinitialresultsfromthePhase1aSTAR-0215trialandtheanticipatednatureandtimingofreceiptofthedatafromthetwoadditional cohortsinsuchtrial;expectationsr ...

STAR-0215 Development and Trials - STAR-0215 is a potential best-in-class monoclonal antibody for treating hereditary angioedema (HAE), aiming for long-acting, effective attack prevention with dosing every three months or potentially less frequently[17]. - The Phase 1a clinical trial of STAR-0215 showed it was well tolerated at all dose levels (100mg, 300mg, and 600mg) with no serious adverse events and an estimated half-life of up to 117 days[19]. - Initial results from the Phase 1a trial support the potential for less frequent dosing, with evaluations for 6-month dosing expected in Q4 2023[19]. - The Phase 1b/2 trial, ALPHA-STAR, initiated in February 2023, will evaluate safety, tolerability, and quality of life in HAE patients, with initial results expected in mid-2024[20]. - STAR-0215 aims to normalize the lives of people living with HAE by providing a first-choice preventative treatment option[18]. - STAR-0215 demonstrated a half-life of approximately 117 days, supporting potential dosing every three months or less frequently[27]. - In Phase 1a clinical trials, STAR-0215 was well tolerated with no serious adverse events reported among 25 healthy subjects[27]. - The Phase 1b/2 trial, ALPHA-STAR, initiated in February 2023, will evaluate safety, tolerability, and efficacy in patients with HAE, with initial results expected in mid-2024[28]. - Preclinical studies indicated STAR-0215 has a three to four-fold longer half-life compared to lanadelumab, suggesting a significantly longer duration of action[29]. - STAR-0215's preclinical data supports its potential as a preventative therapy for HAE, with the possibility of less frequent dosing[29]. - The company plans to evaluate the potential for 6-month dosing in additional cohorts during the Phase 1a trial, with initial results expected in Q4 2023[27]. - STAR-0215 is positioned to compete directly with TAKHZYRO, a monoclonal antibody approved for HAE treatment[34]. - The company plans to develop a drug-device combination for STAR-0215, which may face regulatory hurdles that could delay clinical trials and commercialization[170]. - The success of the company’s business and future revenue generation is contingent upon the successful development and commercialization of STAR-0215, which may never occur[171]. - Clinical trials are lengthy, expensive, and uncertain, with potential for significant delays or failures impacting the development timeline of STAR-0215[178]. - The company has limited experience in designing clinical trials, which may hinder the ability to support marketing approval for STAR-0215[173]. - Adverse events or unexpected properties of STAR-0215 could delay or prevent marketing approval, impacting the company's business prospects[181]. - The company may face unforeseen events during clinical trials that could delay or prevent marketing approval for STAR-0215[182]. - The company is facing potential delays in clinical trials due to various factors, which could harm the commercial prospects for its product candidates and delay revenue generation[184]. - The company plans to conduct clinical trials outside the United States, which may be affected by global instability and other unforeseen risks[185]. - Delays in patient enrollment for clinical trials could significantly impact the timing of necessary regulatory approvals and the overall development process[187]. - STAR-0215's success will depend on its efficacy, safety, dosing frequency, and pricing compared to existing therapies[193]. - The company may face substantial competition from larger pharmaceutical and biotechnology firms, which could affect its operating results[192]. - Changes in product candidate manufacturing or formulation may lead to increased costs and delays in clinical trials[191]. - The company has limited financial and managerial resources, focusing on the development of STAR-0215, which may limit its ability to pursue other potentially profitable opportunities[202]. - The enrollment and retention of patients in clinical trials may be affected by perceptions of STAR-0215's advantages over existing therapies[197]. - The company may need to amend clinical trial protocols in response to regulatory feedback, which could result in additional costs and delays[186]. - The company has never obtained marketing approval for any product candidate, which poses a risk to future revenue generation[208]. - There is a global shortage of non-human primates for drug development, potentially increasing preclinical development costs and causing delays[206]. - The company may face delays in clinical trials if additional preclinical studies are required by the FDA or other regulatory authorities[206]. - Future research programs to identify new product candidates will require substantial resources, and failure to identify suitable compounds could harm the financial position[207]. - Approval of any marketing applications may be delayed by several years if additional studies are required by regulatory authorities[209]. - Delays in obtaining marketing approvals could prevent commercialization of STAR-0215 or future product candidates, impacting profitability[210]. - The company cannot predict the timely completion or outcome of preclinical testing, which may affect the submission of INDs or similar applications[206]. - The company may be forced to abandon development efforts for STAR-0215 or future candidates if marketing approvals are not obtained[210]. - There is uncertainty regarding the acceptance of clinical programs by the FDA or comparable foreign regulatory authorities[206]. - The company has not succeeded in demonstrating efficacy and safety in Phase 3 clinical trials for any product candidates[208]. Market Opportunity and Competition - The global market for HAE therapies is strong and growing, with an unmet medical need for potent and long-duration preventative therapies[18]. - Current FDA-approved therapies for HAE have limitations in dosing frequency and side effects, indicating a market opportunity for STAR-0215[24]. - Market research indicates strong interest from U.S. physicians and HAE patients for a product with the potential profile of STAR-0215[26]. - The estimated prevalence of Type I and Type II HAE ranges from 1 in 10,000 to 1 in 50,000, with fewer than 8,000 patients in the U.S. and 15,000 in Europe[22]. - The company is developing STAR-0215 for the treatment of HAE, competing against four FDA-approved therapies for on-demand treatment and four for long-term prevention[193]. Regulatory Environment - Regulatory processes for drug approval require substantial time and financial resources, impacting the company's operational strategy[49]. - The FDA's approval process for drugs involves multiple stages, including preclinical studies, IND submission, and clinical trials, which are critical for market entry[50][52]. - The company must submit progress reports detailing clinical trial results to the FDA at least annually, ensuring compliance with safety and efficacy standards[68]. - The recent Food and Drug Omnibus Reform Act mandates the development of diversity action plans for Phase 3 clinical trials to enhance patient population diversity[67]. - Expanded access programs allow investigational drugs to be used outside clinical trials for patients with serious conditions when no satisfactory alternatives exist[59][60]. - The company is required to comply with post-approval requirements, including potential Risk Evaluation and Mitigation Strategies (REMS) for newly approved products[52]. - Clinical trials are divided into four phases, with Phase 3 trials typically required for marketing approval, emphasizing the need for robust data collection[65][66]. - The FDA's application user fee for federal fiscal year 2023 is approximately $3.25 million, with an annual program fee exceeding $394,000 per eligible prescription product[77]. - The FDA aims to review 90% of applications for New Molecular Entities (NMEs) within ten months and 90% of priority review applications within six months[79]. - A Complete Response Letter (CRL) indicates that the application will not be approved in its current form, outlining deficiencies that may require substantial additional testing or information[84]. - The FDA may require post-approval trials and monitoring programs to assess a product's safety after commercialization, which can affect market potential and profitability[86]. - The FDA's regulations mandate that pharmaceutical products be manufactured in approved facilities and in compliance with current Good Manufacturing Practices (cGMPs)[71]. - The failure to submit clinical trial information to clinicaltrials.gov can result in civil monetary penalties of up to $10,000 for each day the violation continues[69]. - The FDA's review process includes inspections of manufacturing facilities and clinical sites to ensure compliance with regulatory standards[80][81]. - The Pediatric Research Equity Act requires sponsors to submit a pediatric study plan before submitting required data, ensuring safety and effectiveness for pediatric populations[73]. - The FDA may grant deferrals for pediatric data submission until after adult approval, based on specific criteria[75]. - The PREVENT Pandemics Act clarifies that foreign drug manufacturing establishments must register with the FDA, even if further processing occurs outside the U.S.[71]. - The FDA aims to complete its review of priority review applications within six months, compared to ten months for standard review[91]. - Accelerated approval allows drug products to be approved based on surrogate endpoints that predict clinical benefits, with post-marketing trials required[92]. - The FDORA mandates that sponsors of accelerated approval products submit progress reports on post-approval studies every six months[93]. - Regenerative advanced therapies can receive expedited development and review, with potential eligibility for priority review and accelerated approval[94]. - The Rare Pediatric Disease Priority Review Voucher program allows sponsors to receive a voucher for priority review of a subsequent application upon approval of a rare pediatric disease product[96]. - The FDA may only award a rare pediatric disease PRV if the product is designated before September 30, 2024, and approved before September 30, 2026[98]. - The Hatch-Waxman Act allows for the approval of generic drugs that are bioequivalent to previously approved drugs, with a five-year exclusivity period for new chemical entities[107]. - The BPCIA provides an abbreviated approval pathway for biosimilars, with a 12-year exclusivity period for reference products[110]. - Orphan drug designation provides advantages such as tax benefits and seven years of exclusivity for the first approved product for a rare disease[112]. - Orphan drug exclusivity does not prevent the approval of a different product for the same rare disease under certain conditions[113]. - The Court of Appeals for the 11th Circuit ruled that orphan drug exclusivity applies to the entire designated disease or condition, not just the indication or use[114]. - Pediatric exclusivity can provide an additional six months of regulatory exclusivity for drug products if pediatric data is submitted in response to FDA requests[115]. - Patent term restoration under the Hatch-Waxman Act allows for a limited extension of up to five years for patents lost during product development and FDA review[117]. - The new Clinical Trials Regulation in the EU simplifies the approval process, requiring only a single application for trials conducted in multiple Member States[119]. - The centralized procedure in the EU allows for a maximum evaluation timeframe of 210 days for marketing authorization applications, with accelerated evaluation possible in exceptional cases[126]. - Conditional marketing authorization can be granted for products intended to meet unmet medical needs, allowing market access before comprehensive clinical data is available[129]. - New chemical entities in the EU qualify for eight years of data exclusivity and an additional two years of market exclusivity upon marketing authorization[131]. - Pediatric studies conducted in accordance with a Pediatric Investigation Plan can lead to a six-month extension of protection under a supplementary protection certificate[132]. - Orphan medicinal products can receive designation if they target conditions affecting not more than five in ten thousand persons in the EU[133]. - Orphan medicinal products receive ten years of market exclusivity in the EU, with potential reduction to six years if proven sufficiently profitable[134]. - Marketing authorization for similar products can occur during the exclusivity period if they demonstrate clinical superiority or if the original product cannot meet market demand[135]. - The UK is no longer part of the EU's centralized marketing authorization process, requiring separate approvals for product candidates in the UK[138]. - The MHRA oversees medicines in Great Britain, while Northern Ireland remains under EU regulations[136]. Financial and Operational Risks - The company faces risks related to compliance with evolving privacy and data security laws, which could impact operations and financial results[164]. - The company operates in a dynamic environment with substantial risks that could affect financial performance and stock price[167]. - The company must navigate complex healthcare laws and regulations that may constrain business arrangements and impact financial outcomes[160]. - The company has limited financial and managerial resources, focusing on the development of STAR-0215, which may limit its ability to pursue other potentially profitable opportunities[202]. - The ACA and subsequent legislation have led to Medicare payment reductions of up to 4%, affecting potential revenue from product candidates[147]. - Recent legislation has delayed the 4% Medicare sequester until the end of 2024, impacting healthcare funding[148]. - Proposed regulations aim to bring transparency to pharmaceutical pricing and reduce costs under Medicare and Medicaid[151]. - The Inflation Reduction Act (IRA) requires manufacturers to negotiate prices for certain drugs with Medicare starting in 2026, impacting 10 high-cost drugs initially[154]. - Medicare out-of-pocket drug costs will be capped at an estimated $4,000 in 2024 and $2,000 in 2025, shifting some cost-sharing to drug manufacturers[155]. - The IRA imposes penalties on drug manufacturers for non-compliance with negotiated prices and requires rebates for price increases exceeding inflation[155]. - Individual states are increasingly implementing regulations to control pharmaceutical pricing, which may affect demand and pricing pressures for products[157]. - In the European Union, pricing and reimbursement schemes vary, with some countries requiring cost-effectiveness studies for drug approval[158]. - The California Consumer Privacy Act (CCPA) and the California Privacy Rights Act (CPRA) impose significant compliance requirements on businesses handling personal information[163]. - The company is developing STAR-0215 for the treatment of HAE, competing against four FDA-approved therapies for on-demand treatment and four for long-term prevention[193].

Clinical Development - STAR-0215 is in clinical development for hereditary angioedema (HAE) and aims to provide long-acting treatment with dosing every three months or longer [81]. - The Phase 1a clinical trial for STAR-0215 enrolled 24 healthy subjects, with doses of 100mg, 300mg, and 600mg administered subcutaneously [82]. - The company anticipates significant increases in research and development expenses in the upcoming quarters related to STAR-0215 [93]. - Future funding requirements will depend on various factors, including the progress and costs of clinical trials for STAR-0215 and other product candidates [124]. Financial Performance - The company reported net losses of $38.6 million for the nine months ended September 30, 2022, compared to $209.9 million for the same period in 2021 [87]. - Net loss for the three months ended September 30, 2022, was $12.0 million, compared to a net loss of $7.9 million for the same period in 2021, reflecting an increase of $4.1 million [102]. - As of September 30, 2022, the company had an accumulated deficit of $494.4 million [87]. - Other income, net increased by $595,000 to $642,000 for the nine months ended September 30, 2022, primarily due to higher yields on interest-earning assets [111]. Research and Development Expenses - Research and development expenses for STAR-0215 were $14.6 million for the nine months ended September 30, 2022, compared to $4.4 million for the same period in 2021, reflecting a significant increase [92]. - Total research and development expenses for the company were $24.7 million for the nine months ended September 30, 2022, up from $9.9 million in the prior year [92]. - Research and development expenses increased by $3.9 million to $7.7 million for the three months ended September 30, 2022, representing a 103% increase compared to the same period in 2021 [104]. - For the nine months ended September 30, 2022, research and development expenses increased by $14.8 million to $24.7 million, a 150% increase from $9.9 million in the same period in 2021 [108]. Cash and Funding - The company had $116.6 million in cash, cash equivalents, and short-term investments as of September 30, 2022 [87]. - As of September 30, 2022, the company had cash, cash equivalents, and short-term investments totaling $116.6 million, expected to support operations into mid-2024 [112]. - The company reported cash, cash equivalents, and short-term investments totaling $116.6 million as of September 30, 2022, with an additional $12.7 million raised under the Jefferies ATM Program expected to support operations into mid-2024 [123]. - The company expects to require substantial additional funding to complete the development and commercialization of STAR-0215 and support ongoing operations [87]. Operational Challenges - The company anticipates fluctuations in results of operations due to factors such as research and development progress and regulatory submission outcomes [101]. - The company may be required to delay or reduce product development efforts if additional funds are not secured in a timely manner [128]. - The company does not have any committed external sources of funds and may need to raise capital through equity offerings, debt financings, or collaborations [126]. - If additional capital is raised through equity or convertible debt, stockholders' ownership interests may be diluted [127]. - Debt financing, if available, could impose periodic payment obligations and restrictive covenants that may limit the company's operational flexibility [127]. - Collaborations or licensing arrangements may require the company to relinquish valuable rights to technologies or future revenue streams [128].

Clinical Development - STAR-0215 is in clinical development for hereditary angioedema (HAE) with a potential dosing regimen of once every three months or longer[84]. - The Phase 1a clinical trial for STAR-0215 is evaluating safety and pharmacokinetics with preliminary results anticipated by year-end 2022[85]. - The company plans to initiate a Phase 1b/2 trial in participants with HAE in 2023, assuming positive data from the Phase 1a trial[85]. Financial Performance - The company reported net losses of $26.6 million for the six months ended June 30, 2022, compared to $177.6 million for the same period in 2021[91]. - Net loss for the six months ended June 30, 2022, was $26.6 million, a decrease of $150.9 million from a net loss of $177.5 million for the same period in 2021[113]. - Other income, net increased by $234,000 to $253,000 for the six months ended June 30, 2022, from $19,000 for the same period in 2021, mainly due to higher yields on interest-earning assets[115]. Research and Development Expenses - Research and development expenses for STAR-0215 were $10.1 million for the six months ended June 30, 2022, significantly up from $2.9 million in the same period of 2021[96]. - Total research and development expenses for the six months ended June 30, 2022, were $17.0 million, compared to $6.1 million in the same period of 2021[96]. - Research and development expenses increased by 180% to $17.0 million for the six months ended June 30, 2022, compared to $6.1 million for the same period in 2021[112]. - Research and development expenses for the three months ended June 30, 2022, increased by 90% to $6.6 million from $3.5 million for the same period in 2021[108]. Cash and Investments - The company had $102.5 million in cash, cash equivalents, and short-term investments as of June 30, 2022, expected to support operations through 2023[91]. - Cash, cash equivalents, and short-term investments totaled $102.5 million as of June 30, 2022, expected to support operating expenses through 2023[116]. - As of June 30, 2022, the company had available cash, cash equivalents, and short-term investments of $102.5 million, expected to support operating expenses and capital expenditures through 2023[126]. Operating Expenses - General and administrative expenses rose by 43% to $9.9 million for the six months ended June 30, 2022, from $6.9 million for the same period in 2021[114]. - The total operating expenses for the six months ended June 30, 2022, were $26.8 million, a decrease of $150.7 million compared to $177.6 million for the same period in 2021, primarily due to the absence of acquired in-process research and development expenses[113]. - General and administrative expenses for the three months ended June 30, 2022, increased by 21% to $4.8 million from $4.0 million for the same period in 2021[109]. Funding and Capital Requirements - The company anticipates needing substantial additional funding to complete the development and commercialization of STAR-0215 and future product candidates[117]. - The company raised an aggregate of $426.0 million through various financing activities since inception, with net proceeds of approximately $104.3 million from the February 2021 Financing[116][118]. - The company may need to seek additional funds sooner than planned due to uncertainties in research, development, and commercialization of biotechnology products[127]. - Future funding requirements will depend on various factors, including clinical trial progress and regulatory approval outcomes[127]. - The company does not have any committed external source of funds and may rely on equity offerings, debt financings, and collaborations for financing[129]. - If additional capital is raised through equity or convertible debt, stockholders' ownership interests may be diluted[129]. - The company may have to relinquish valuable rights to technologies or future revenue streams if funds are raised through collaborations or licensing arrangements[130]. Impact of COVID-19 - The impact of the COVID-19 pandemic on operations and business prospects remains a concern for future funding and development efforts[127].

Acquisition and Development - The company acquired Quellis Biosciences, Inc. in January 2021, resulting in gross proceeds of approximately $110.0 million from a private placement in February 2021[26]. - The company is currently focused on the development of STAR-0215 as a potential treatment for HAE, which is in preclinical development[165]. - The company has completed cell line development for STAR-0215 and is in the process of manufacturing sufficient material for nonclinical and clinical needs[53]. - The company relies on third-party manufacturers for the production of STAR-0215 and has no plans to build its own manufacturing facilities[52]. - The company has identified a cell line for STAR-0215 that can generate sufficient material for preclinical and clinical studies, with plans for Good Manufacturing Practices manufacturing[19]. STAR-0215 Clinical Trials - STAR-0215 is designed to be a best-in-class monoclonal antibody for treating Hereditary Angioedema (HAE), with a projected dosing frequency of once every three months or longer[27]. - The company plans to submit an Investigational New Drug application for STAR-0215 in mid-2022 and initiate a Phase 1a clinical trial shortly thereafter, with initial results anticipated by year-end 2022[27]. - The Phase 1a trial aims to establish safety, tolerability, and prolonged half-life of STAR-0215, with a focus on inhibiting plasma kallikrein activity[40]. - If positive data is obtained from the Phase 1a trial, the company plans to initiate a Phase 1b/2 trial in patients with HAE in 2023[39]. - The Phase 1b/2 trial in patients with HAE is expected to be a randomized, placebo-controlled, global multi-center trial, aiming to demonstrate safety, tolerability, and inhibition of plasma kallikrein activity[27]. Market Potential and Competition - The global market for HAE therapy is strong and growing, with an estimated prevalence of Type I and Type II HAE ranging from 1 in 10,000 to 1 in 50,000, translating to fewer than 8,000 patients in the U.S. and 15,000 in Europe[32]. - STAR-0215 will compete directly with TAKHZYRO, a monoclonal antibody approved for HAE, which is administered every two weeks[45]. - The company anticipates that positive data from clinical trials could establish STAR-0215 as a differentiated treatment option in the HAE market[19]. - The approved preventative therapies for HAE have limitations in dosing frequency and side effects, indicating a significant unmet medical need for more effective treatments[36]. Regulatory and Compliance - The FDA requires completion of preclinical laboratory tests in compliance with GLP regulations before a sponsor can initiate clinical trials[58]. - An IND must be submitted to the FDA, which includes a protocol for each clinical trial and results of preclinical tests, before human trials can begin[60]. - The FDA imposes a 30-day waiting period after filing an IND to review the application and ensure safety for human subjects[60]. - Clinical trials are divided into four phases, with Phase 1 focusing on safety and dosage, Phase 2 on effectiveness, Phase 3 on further evaluation in larger populations, and Phase 4 on post-approval studies[72][73]. - The FDA mandates that clinical trial information be registered on clinicaltrials.gov, with non-compliance potentially resulting in civil penalties of up to $10,000 per day[75]. Financial and Operational Risks - The company has limited financial and managerial resources, focusing on STAR-0215 as a potential treatment for HAE, a rare disease with unmet medical needs[174]. - The company acknowledges that the development timeline for STAR-0215 could take years, with significant uncertainty regarding its safety and efficacy[168]. - Delays in patient enrollment for clinical trials could hinder the receipt of necessary regulatory approvals, impacting the timeline for product candidates like STAR-0215[187]. - The company faces challenges in enrolling sufficient patients for clinical trials due to factors such as the rarity of diseases, competition for patients, and existing treatment options[190]. - The COVID-19 pandemic has caused significant disruptions, potentially delaying clinical trials and increasing costs, while also impacting the financial markets and the company's ability to raise capital[195]. Marketing and Commercialization - The company currently lacks a formal sales and marketing infrastructure, which is essential for the successful commercialization of approved products[209]. - The company plans to retain full commercialization rights for products that can be marketed with a specialized sales force and seek co-promotion rights when feasible[210]. - Establishing sales, marketing, and distribution capabilities will require substantial resources and may delay product launches, potentially leading to significant costs[211]. - Failure to establish sales and marketing capabilities could adversely affect the commercialization of approved product candidates[213]. - The potential market opportunities for product candidates are difficult to estimate, and inaccuracies in assumptions could lead to smaller actual markets than projected[208].

Financial Data and Key Metrics Changes - As of September 30, 2021, the company had cash and cash equivalents of $131.8 million, expected to fund operations through 2023 [27] - R&D expenses decreased to $3.8 million in Q3 2021 from $7.8 million in Q3 2020, while G&A expenses increased to $4.1 million from $3.1 million in the same period [27] - The operating loss was $7.9 million in Q3 2021, compared to $10.9 million in Q3 2020, with a net loss of $7.9 million or $0.61 per share [27] Business Line Data and Key Metrics Changes - The lead program, STAR-0215, is a monoclonal antibody aimed at treating hereditary angioedema (HAE), with initial clinical trial results expected by the end of 2022 [8][9] - STAR-0215 is designed to be a patient-friendly preventative therapy, with a potential for infrequent dosing due to its extended half-life [14][23] Market Data and Key Metrics Changes - The global market for HAE treatments is projected to grow from $2 billion in 2020 to over $4.5 billion by 2026, indicating a significant opportunity for STAR-0215 [11] - Approximately 8,000 people are affected by HAE in the United States, with a substantial unmet need for effective preventative treatments [11] Company Strategy and Development Direction - The company aims to develop therapeutics that address unmet needs in rare and niche allergic and immunological diseases, with a focus on patient-friendly treatment options [28] - The strategy includes evaluating opportunities to expand the pipeline while maintaining a focus on the HAE community's needs [28] Management's Comments on Operating Environment and Future Outlook - Management emphasized the importance of reducing both disease and treatment burden for HAE patients, aiming for a product that offers robust efficacy with infrequent dosing [34] - The company is on track to file an IND for STAR-0215 in mid-2022 and initiate clinical trials shortly thereafter, with a focus on establishing a differentiated profile [21][42] Other Important Information - STAR-0215 has shown a tenfold improvement in potency over existing treatments in preclinical studies, with a potential for a longer duration of action due to YTE modifications [15][17] - The company is working with a CDMO to ensure efficient development and commercialization of STAR-0215 [21] Q&A Session Summary Question: Could biomarkers from the Phase 1 study serve as markers for accelerated approval? - Management confirmed that pharmacodynamic markers will be incorporated into the Phase 1 study to chart the path for future phases and regulatory strategy [32][33] Question: What is the balance between decreasing attacks and increasing time between dosing? - Management noted that patients want to decrease disease burden while also reducing treatment burden, emphasizing the importance of both factors in their product development [34][36] Question: When will full data from Phase 1 be available? - Initial results from the Phase 1 study are expected by the end of 2022, with a long follow-up period to assess safety and pharmacokinetics [41][42] Question: What attributes of STAR-0215 might help avoid concerns about prophylactic therapy efficacy? - Management highlighted the goal of maintaining a high level of plasma kallikrein inhibition for longer durations to alleviate patient anxiety about potential attacks [52][54] Question: How does the company view the competitive landscape for prophylactic treatments? - Management acknowledged the evolving landscape with various modalities and emphasized STAR-0215's differentiated profile as a trusted monoclonal antibody with potential for infrequent dosing [56] Question: What are the company's plans for pipeline expansion? - The company is open to evaluating opportunities in related areas of allergy and immunology, aiming to optimize its organizational structure while making a significant difference for patients [59]