Expression data from patient-derived xenograft (PDX) mouse models exposed to micvotabart pelidotin (MICVO) indicate gene signatures associated with efficacy, deepening understanding of MOA and potential patient response Combination of a mouse analog of MICVO and a mouse anti-PD-1 therapy in a syngeneic model resulted in significantly greater tumor regression than either treatment alone Company advances MICVO into monotherapy and combination clinical trials with Merck's anti-PD-1 therapy, Keytruda® (pembroli ...

Product Development - Pyxis Oncology's lead product candidate, micvotabart pelidotin, targets EDB+FN, a component highly expressed in various solid tumors, aiming to destabilize tumor structure while sparing healthy cells [19]. - The company aims to prioritize development efforts towards R/M HNSCC, with an estimated one million new cases worldwide annually by 2030 [36]. - The company initiated the dose expansion phase (Part 2) of the PYX-201-101 study, focusing on R/M HNSCC patients, expecting preliminary data in the second half of 2025 [30]. - The company aims to address the unmet need for more efficacious therapies in R/M HNSCC, particularly those that are chemotherapy-free and have superior tolerability [41]. - The company has deprioritized certain clinical programs and assets to focus resources on the development of micvotabart pelidotin [94]. Clinical Trials - In the Phase 1 dose escalation study (PYX-201-101), 80 patients were dosed, with a confirmed 50% objective response rate (ORR) in R/M HNSCC patients at the therapeutically active dose range of 3.6 mg/kg – 5.4 mg/kg IV Q3W [24][25]. - The study observed tumor regression across nine solid tumor types, with a 26% ORR in six solid tumor types of interest at the same dose range [25]. - The Phase 1 trial of micvotabart pelidotin (PYX-201-101) enrolled 80 patients, with a therapeutically active dose response range identified between 3.6 mg/kg and 5.4 mg/kg IV Q3W [55]. - The preliminary efficacy analysis included 65 patients, showing evidence of tumor regression across all nine solid tumor types, with a 26% overall response rate (ORR) in six solid tumor types at the therapeutic dose range of 3.6 mg/kg – 5.4 mg/kg IV Q3W [71]. - The study achieved a confirmed 50% overall response rate (ORR) in patients with R/M HNSCC, with a disease control rate (DCR) of 100% based on RECIST 1.1 criteria [78]. Safety and Efficacy - Preliminary data from the Phase 1 trial indicated a manageable safety profile, with 52% of patients dosed at the 5.4 mg/kg level [55]. - Micvotabart pelidotin demonstrated a favorable safety profile, with only 1 patient discontinuing due to treatment-related adverse effects (TRAEs) and no Grade 5 TRAEs observed [62]. - The trial reported a 0% incidence rate of Grade 3 and 4 TRAEs in the therapeutic dose range of 3.6 mg/kg – 5.4 mg/kg IV Q3W [64]. - The median duration of response in efficacy evaluable patients was 115 days (16 weeks) as of the data cut-off date of October 4, 2024 [78]. - The drug's pharmacokinetic profile showed high systemic bioavailability and stability in circulation, differentiating it from other approved antibody-drug conjugates (ADCs) [60]. Regulatory Designations - The FDA granted Fast Track Designation to micvotabart pelidotin for treating adult patients with R/M HNSCC whose disease progressed after platinum-based chemotherapy and anti-PD-(L)1 therapy [27]. - The FDA granted Fast Track Designation for micvotabart pelidotin for treating adults with R/M HNSCC in February 2025 [203]. - In May 2023, the FDA granted Orphan Drug Designation for micvotabart pelidotin in the treatment of pancreatic cancer [208]. - Orphan Drug Designation provides seven years of market exclusivity if no same drug was previously approved for the same orphan condition [207]. Collaborations and Partnerships - A Clinical Trial Collaboration and Supply Agreement was established with Merck for a study of micvotabart pelidotin in combination with KEYTRUDA® [31]. - The company is actively engaging with potential partners to monetize its intellectual property estate, including inactive programs and biologics technology platforms [37]. - The company has entered into a license agreement with the University of Chicago, which includes potential development and commercial milestones of up to $7.7 million and annual maintenance fees starting at $10,000 [118]. - The company has entered into a license agreement with Biosion USA, Inc. for the development and commercialization rights for a Siglec-15 targeting antibody, now referred to as PYX-106 [126]. Market and Competitive Landscape - The company faces competition from major pharmaceutical and biotechnology companies, as well as alternative therapeutic modalities such as cell therapies and bispecific antibodies [109]. - The company has significant competition in the HNSCC indication, with notable competitors including Merus and Bicara targeting similar patient populations [111]. - Head and Neck Cancer (HNC) accounts for approximately 4.5% of global cancer diagnoses, with an estimated 1,464,550 new cases and 487,993 deaths in 2020 [38]. - In the U.S., there are approximately 59,000 cases of HNSCC annually, with a 13% 5-year survival rate in the R/M (Stage IVC) setting [39]. Financial Obligations and Fees - Under the Pfizer License Agreement, the company is obligated to pay up to $665 million in future contingent payments for the first four licensed ADCs, along with tiered royalties on net sales ranging from low single digits to mid-teens [123]. - The company paid an upfront fee of $10.0 million under the Biosion License Agreement and is obligated to pay up to $217.5 million in future contingent payments for normal approval and $222.5 million for Accelerated Approval [127]. - The cost of preparing and submitting a BLA is substantial, with a user fee of $4,310,002 for BLAs requiring clinical data for fiscal year 2025 [212]. - Annual program fees for each prescription product under an approved BLA are currently $403,889 for fiscal year 2025 [212]. Intellectual Property - The company has a patent portfolio comprising 33 different patent families, including those directed to compositions of matter for antibodies and antibody-drug conjugates [146]. - The patent family for micvotabart pelidotin includes granted patents in multiple countries, with a 20-year term running through 2037, absent any available patent term adjustments [149]. - The company has sole ownership of a patent family for dosage and treatment regimens of micvotabart pelidotin, with a provisional patent application filed in the United States, running through 2045 [152]. - The company has exclusively licensed a patent family related to cytotoxic peptides and antibody-drug conjugates from Pfizer, with granted patents in multiple countries and a 20-year term running through 2032 [153]. - The company has acquired a patent family for anti-CD123 antibody-drug conjugates, with granted patents in several countries and a term running through 2038 [156].

Financial Performance - The company reported a net loss of $77.3 million, or ($1.32) per common share, for the year ended December 31, 2024, compared to a net loss of $73.8 million, or ($1.85) per common share, in 2023[12]. - Total revenues for 2024 were $16.1 million, including $8.1 million in royalty revenues and $8.0 million from the sale of royalty rights[15]. - Research and development expenses increased to $58.7 million for the year ended December 31, 2024, compared to $49.6 million in 2023, primarily due to clinical trial-related expenses[12]. - General and administrative expenses decreased to $25.4 million in 2024 from $32.6 million in 2023, attributed to lower employee costs and reduced legal and consulting fees[12]. - A workforce reduction of approximately 20% was implemented to streamline operations and focus resources on the micvotabart pelidotin clinical program[7]. Cash and Assets - As of December 31, 2024, Pyxis Oncology had cash and cash equivalents of $128.4 million, sufficient to fund operations into the second half of 2026[12]. - Total current assets increased to $132,440 million in December 2024, up from $124,604 million in December 2023, representing a growth of 6.5%[17]. - Cash and cash equivalents rose significantly to $19,473 million, compared to $9,664 million in the previous year, marking an increase of 101.4%[17]. - Total assets decreased to $157,181 million from $173,726 million, a decline of 9.6%[17]. - Total stockholders' equity slightly decreased to $120,751 million from $125,704 million, reflecting a decline of 4.0%[17]. Liabilities and Deficits - Total liabilities decreased to $36,430 million in December 2024 from $48,022 million in December 2023, a reduction of 24.2%[17]. - Accounts payable increased to $4,859 million, up from $3,896 million, indicating a rise of 24.6%[17]. - Accumulated deficit widened to $(363,556) million in December 2024 from $(286,225) million in December 2023, an increase of 27.1%[17]. - Operating lease liabilities, net of current portion, decreased to $18,650 million from $20,099 million, a decrease of 7.2%[17]. - Deferred revenues were reported as zero in December 2024, down from $7,660 million in December 2023[17]. Clinical Developments - Pyxis Oncology achieved a confirmed 50% objective response rate in its Phase 1 trial of micvotabart pelidotin for recurrent and metastatic head and neck squamous cell carcinoma[4]. - The company received Fast Track Designation from the FDA for micvotabart pelidotin targeting adult patients with recurrent and metastatic head and neck squamous cell carcinoma[4]. - Preliminary data from ongoing trials of micvotabart pelidotin are expected in the second half of 2025 and the first half of 2026[4]. - The company recorded a non-cash impairment loss of $21.0 million related to in-process research and development intangible asset for PYX-107[12].

Core Insights - The company has reported positive preliminary data from the Phase 1 dose escalation trial of micvotabart pelidotin (MICVO), achieving a confirmed 50% objective response rate in recurrent and metastatic head and neck squamous cell carcinoma (R/M HNSCC) [1][6] - MICVO has received Fast Track Designation from the U.S. FDA for treating adult patients with R/M HNSCC whose disease has progressed after platinum-based chemotherapy and anti-PD-(L)1 therapy [1][10] - The company has initiated monotherapy expansion cohorts for MICVO in 2L and 3L R/M HNSCC patients, with preliminary data expected in 2H25 and 1H26 [1][7] Pipeline Updates - The lead therapeutic candidate, micvotabart pelidotin, has shown significant tumor regression in multiple tumor types during the Phase 1 dose escalation study [4] - A combination study of MICVO with Merck's anti-PD-1 therapy, KEYTRUDA®, has been initiated, with preliminary data expected in 2H25 [5][7] - The company has streamlined its organization and reduced its workforce by approximately 20% to focus resources on the MICVO clinical program [5][8] Financial Overview - As of December 31, 2024, the company had cash and cash equivalents of $128.4 million, sufficient to fund operations into the second half of 2026 [11] - Research and development expenses increased to $58.7 million in 2024 from $49.6 million in 2023, primarily due to clinical trial-related expenses [11] - The net loss for the year ended December 31, 2024, was $77.3 million, or $1.32 per common share, compared to a net loss of $73.8 million, or $1.85 per common share, in 2023 [11][16]

Company Overview - Pyxis Oncology, Inc. is a clinical-stage company focused on developing next-generation therapeutics for difficult-to-treat cancers [3] - The company is working on PYX-201, an antibody-drug conjugate (ADC) targeting EDB+FN, which is currently in Phase 1 clinical studies for various solid tumors [3] Upcoming Events - Lara S. Sullivan, M.D., President and CEO of Pyxis Oncology, will participate in a fireside chat at the Leerink Partners Global Healthcare Conference on March 10, 2025, at 2:20 PM EST [1] - A live webcast and replay of the fireside chat will be available on the company's Investor Relations website [2]

Core Insights - Pyxis Oncology, Inc. has received Fast Track Designation from the FDA for its drug PYX-201, aimed at treating recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC) in patients who have progressed after platinum-based chemotherapy and anti-PD-(L)1 therapy [1][2] Company Overview - Pyxis Oncology is a clinical-stage company focused on developing next-generation therapeutics for challenging cancers, with PYX-201 being its lead clinical candidate [8] - PYX-201 is an antibody-drug conjugate (ADC) that targets Extradomain-B Fibronectin (EDB+FN), a component of the tumor extracellular matrix, designed to kill cancer cells and address tumor microenvironment factors [5][8] Industry Context - Head and Neck Cancer (HNC) is the sixth most common cancer globally, with approximately 1,464,550 new cases and 487,993 deaths annually [3] - Nearly 50% of HNSCC cases progress to recurrent or metastatic stages post-initial treatment, with a median overall survival of less than one year [3] - The incidence of HNSCC is projected to increase by 30% annually by 2030, driven by factors such as tobacco use, alcohol consumption, and HPV infections [3]

Core Insights - Pyxis Oncology, Inc. is making significant progress in its clinical program for PYX-201, an antibody-drug conjugate (ADC) targeting Extradomain-B Fibronectin (EDB+FN), which is highly expressed in various tumor types [1][10] - The company is actively recruiting for two trials: one evaluating PYX-201 as a monotherapy for recurrent/metastatic head and neck squamous cell carcinoma (HNSCC) and another combining PYX-201 with Merck's KEYTRUDA® in patients with advanced solid tumors [2][3] Clinical Trials - The Phase 1/2 combination study, PYX-201-102, is set to initiate patient dosing in Q1 2025, focusing on the combination of PYX-201 with pembrolizumab across multiple indications [3][6] - The ongoing Phase 1 PYX-201-101 study has begun enrolling patients for its monotherapy expansion cohorts, targeting advanced solid tumors predicted to express EDB+FN [5][9] Treatment Potential - PYX-201 is designed to deliver its AUR-0101 payload specifically within the tumor microenvironment, potentially enhancing the efficacy of pembrolizumab by allowing T cells to infiltrate challenging tumor microenvironments [3][10] - The ongoing trials represent a critical step in advancing PYX-201 as a potential breakthrough treatment for a broad range of cancers, particularly for patients with limited treatment options [3][11]

Core Insights - Pyxis Oncology, Inc. released preliminary data from a Phase 1 clinical study of PYX-201, showing a 50% objective response rate in Head and Neck Squamous Cell Carcinoma patients [1] - The company has entered a Clinical Trial Collaboration Agreement with Merck to study PYX-201 in combination with Keytruda for various cancers [2] - Analysts have reduced the probability of success for PYX-201 to 10% from 35%, with an updated fair value of $250 million or approximately $4.25 per share [7] Group 1: Clinical Data and Studies - In the ongoing Phase 1 study, among 6 evaluable HNSCC patients treated with PYX-201 at doses of 3.6 – 5.4 mg/kg, there was a confirmed 50% objective response rate, including one complete response and two partial responses [1] - A combination study of PYX-201 and Keytruda is planned for 1L and 2L HNSCC, HR+/HER2- breast cancer, TNBC, and sarcoma, with preliminary data expected in the second half of 2025 [3][5] - Exploratory Phase 1 monotherapy expansion cohorts for PYX-201 are planned for ovarian cancer, NSCLC, HR+/HER2 breast cancer, TNBC, and sarcoma, with preliminary data also expected in the second half of 2025 [4] Group 2: Market and Analyst Insights - William Blair analysts noted that PYX-201 shows limited effectiveness outside of head-and-neck cancer, with only 8.7% of patients responding to the drug at tolerable doses [6] - The stock is expected to trade around $2.80 per share soon, reflecting a valuation of $1.77 per share for PYX-201 and $1.07 for remaining cash by late 2025 [8] - Pyxis has been downgraded to Market Perform due to challenges in differentiating head-and-neck cancer results and modest activity in other solid tumor types [8]

Core Insights - Pyxis Oncology's lead drug candidate, PYX-201, has shown promising preliminary data with a confirmed 50% objective response rate (ORR) in heavily pretreated head and neck squamous cell carcinoma (HNSCC) patients, including one complete response and a 100% disease control rate in a small cohort [1][3] - The overall ORR across six solid tumor types of interest is 26%, indicating dose-dependent responses and supporting the first-in-concept mechanism of the novel extracellular targeting antibody-drug conjugate (ADC) [1][2] - A new clinical trial collaboration agreement with Merck will evaluate the combination of PYX-201 and Merck's anti-PD-1 therapy, KEYTRUDA®, in various cancer types, with dosing expected to begin in the first quarter of 2025 [1][5] Clinical Trial Details - The ongoing Phase 1 clinical trial has enrolled 80 patients across multiple solid tumor types, with doses ranging from 0.3 mg/kg to 8.0 mg/kg, focusing on safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary efficacy [2][4] - The identified dose range for PYX-201 is currently between 3.6 mg/kg and 5.4 mg/kg, with a median of four prior lines of cancer therapies for enrolled patients [2][4] Safety and Pharmacokinetics - PYX-201 has demonstrated a favorable safety profile, with a low incidence of treatment-related adverse events (TRAE) and minimal Grade 3 or Grade 4 TRAEs, indicating its potential for both monotherapy and combination therapy [11][12] - The drug's design allows for increased stability in circulation, attributed to its proprietary site-specific conjugation chemistry [12] Future Development Plans - The company plans to initiate expansion studies for PYX-201 in HNSCC and other solid tumors, with preliminary clinical data expected in the second half of 2025 and early 2026 [7][9][10] - Additional exploratory cohorts are planned for ovarian cancer, non-small cell lung cancer (NSCLC), HR+/HER2- breast cancer, triple-negative breast cancer (TNBC), and sarcoma [9][10] Investor Engagement - Pyxis Oncology will host an investor event to discuss the preliminary Phase 1 data, featuring insights from key physician thought leaders [15][16]

Financial Performance - Pyxis Oncology reported a net loss of $41.8 million for the nine months ended September 30, 2024, compared to a net loss of $58.2 million for the same period in 2023, indicating a reduction in losses year-over-year [59]. - Net loss for the three months ended September 30, 2024, was $21.20 million, a decrease of $1.85 million compared to a net loss of $23.05 million for the same period in 2023 [65]. - Total revenues for the nine months ended September 30, 2024, were $16.1 million, compared to $0 for the same period in 2023, primarily due to a settlement agreement with Novartis [69]. - Other income increased to $7.6 million for the nine months ended September 30, 2024, compared to $6.2 million in 2023, primarily due to higher sublease income [73]. - Other income, net for the three months ended September 30, 2024, was $2.55 million, an increase of $0.25 million compared to $2.30 million for the same period in 2023 [65]. Cash and Investments - As of September 30, 2024, Pyxis Oncology had an accumulated deficit of $328.0 million and cash, cash equivalents, and short-term investments totaling $144.8 million [59]. - As of September 30, 2024, the company had cash, cash equivalents, and short-term investments totaling $144.8 million, with net losses of $21.2 million and $41.8 million for the three and nine months ended September 30, 2024, respectively [74]. - Net cash used in operating activities was $38.4 million for the nine months ended September 30, 2024, compared to $55.5 million in the same period of 2023 [78]. - Net cash used in investing activities was $18.5 million for the nine months ended September 30, 2024, primarily due to purchases of marketable debt securities [79]. - Net cash provided by financing activities was $59.3 million for the nine months ended September 30, 2024, compared to $6.0 million in 2023 [80]. - The company expects existing cash resources to fund operations into the second half of 2026, including clinical development for PYX-201 [80]. Research and Development - The company has not generated any revenues from product sales and does not expect to do so in the foreseeable future, relying instead on research and development agreements for revenue [60]. - Pyxis Oncology's research and development expenses are expected to increase substantially due to ongoing and planned clinical activities [62]. - Research and development expenses increased by $6.7 million, from $37.98 million for the nine months ended September 30, 2023, to $44.72 million for the same period in 2024 [71]. - PYX-201 program-specific research and development costs increased by $12.6 million, primarily due to a $3.2 million increase in clinical trial expenses and a $7.6 million increase in contract manufacturing costs [71]. - Total program costs for the three months ended September 30, 2024, were $11.16 million, significantly up from $4.13 million for the same period in 2023 [66]. Clinical Trials and Product Development - The Phase 1 trial of PYX-201 has dosed 80 subjects, focusing on difficult-to-treat cancers such as head and neck squamous cell carcinoma and non-small cell lung cancer [55]. - PYX-201 received Orphan Drug Designation from the FDA for the treatment of pancreatic cancer, with a starting dose of 0.3 mg/kg in the Phase 1 trial [55]. - The acquisition of Apexigen added PYX-107 to the pipeline, which has shown a 15.2% partial response rate in melanoma patients refractory to anti-PD-(L)1 therapy [59]. - The Phase 1 trial of PYX-106 has dosed 45 subjects, with a starting dose of 0.5 mg/kg and a focus on solid tumors [58]. - The company anticipates announcing preliminary data from the Phase 1 trial of PYX-201 in November 2024 [55]. Expenses and Obligations - General and administrative expenses decreased by $4.7 million, from $10.67 million for the three months ended September 30, 2023, to $6.01 million for the same period in 2024 [68]. - General and administrative expenses decreased by $6.1 million, from $26.5 million in the nine months ended September 30, 2023, to $20.3 million in the same period of 2024 [72]. - Unallocated research and development costs decreased by $8.6 million from $28.2 million for the nine months ended September 30, 2023, to $19.6 million for the same period in 2024 [71]. - The company has contractual lease obligations totaling $27.1 million over the remaining term of its office and laboratory space lease [82].