Zymeworks (ZYME) FY 2025 Conference June 11, 2025 02:00 PM ET Speaker0 Good afternoon, everyone. Thanks so much for being here. My name is Laura Khan. I'm a Vice President in our Healthcare Investment Banking Group. And I'm joined today by Ken Galbraith, CEO of ZymWorks. Ken, thanks so much for being here. Let's go ahead and dive right in. It's of course been an exciting year at ZymWorks. A ton of progress with BTC approval in November for Zahira, and significant progress made on continuing to advance the p ...

Core Viewpoint - Zymeworks Inc. (ZYME) shows potential for significant upside, with a mean price target of $21.35 indicating a 76.7% increase from its current price of $12.08 [1] Price Targets and Estimates - The mean estimate consists of 10 short-term price targets with a standard deviation of $7.45, indicating variability among analysts [2] - The lowest estimate is $12, suggesting a slight decline of 0.7%, while the highest estimate predicts a surge of 148.3% to $30 [2] - Analysts' price targets are often questioned for their reliability, as they may mislead investors rather than provide accurate guidance [3][7] Earnings Estimates and Analyst Agreement - Analysts are optimistic about ZYME's earnings, with a consensus indicating better-than-previously estimated earnings [4] - The Zacks Consensus Estimate for the current year has risen by 6.2% over the past month, with four estimates increasing and no negative revisions [12] - A strong correlation exists between earnings estimate revisions and near-term stock price movements, suggesting potential upside for ZYME [11] Zacks Rank and Investment Potential - ZYME holds a Zacks Rank 2 (Buy), placing it in the top 20% of over 4,000 ranked stocks based on earnings estimate factors [13] - While the consensus price target may not be a reliable indicator of the stock's potential gain, it does provide a directional guide for price movement [13]

Core Insights - Zymeworks Inc. announced the conditional approval of zanidatamab by the National Medical Products Administration (NMPA) in China for treating previously treated, unresectable or metastatic HER2-positive biliary tract cancer (BTC), marking it as the first dual HER2-targeted bispecific antibody approved for this indication in China [1][10] - The approval is a significant advancement for patients with HER2-positive BTC, a group with high unmet medical needs and poor prognoses, and reflects the clinical potential of zanidatamab [2][4] - Zymeworks has received $61 million in upfront and milestone payments from its collaboration partner BeOne Medicines, with an additional $20 million milestone payment linked to the NMPA approval and potential for up to $144 million in further milestones [2][6] Company Overview - Zymeworks is a clinical-stage biotechnology company focused on developing multifunctional biotherapeutics for difficult-to-treat diseases, including cancer, inflammation, and autoimmune diseases [1][6] - The company utilizes its proprietary Azymetric™ technology to engineer and develop zanidatamab, which targets HER2 and induces various mechanisms leading to tumor growth inhibition [5][7] - Zymeworks has strategic partnerships with BeOne Medicines and Jazz Pharmaceuticals, granting exclusive rights for the development and commercialization of zanidatamab in different territories [7] Industry Context - Biliary tract cancers account for approximately 3% of all digestive system tumors, with a rising incidence rate globally, particularly in Asia [4] - Approximately 11%-25.2% of patients with BTC are HER2-positive, making HER2 a validated target for antitumor therapy [4] - Zanidatamab has also received FDA approval in the U.S. and is under regulatory review in the EU, indicating its potential as a best-in-class treatment for HER2-expressing cancers [3][7]

Core Insights - Zymeworks Inc. is advancing its oncology programs with multiple presentations scheduled at major medical conferences, including ASCO and ESMO, highlighting its commitment to developing novel biotherapeutics for difficult-to-treat diseases [1][3][10] Oncology Programs - The company is particularly focused on zanidatamab, which is being presented at ASCO, showcasing long-term outcomes and survival data in HER2-positive gastroesophageal cancer [2][4][6] - Zymeworks' proprietary Azymetric™ platform is emphasized for its ability to develop clinically validated therapeutic antibodies, with zanidatamab being a key example [6][14] Upcoming Presentations - Zymeworks and its partners will present multiple abstracts at the ASCO Annual Meeting from May 31 to June 4, 2025, in Chicago, IL [3] - The ESMO Gynaecological Cancers Congress will also feature a trial-in-progress poster for ZW191, scheduled for June 19-21, 2025, in Vienna, Austria [10] Product Details - Ziihera (zanidatamab-hrii) is a bispecific HER2-directed antibody that has received accelerated approval from the FDA for treating advanced HER2-positive biliary tract cancer [18][34] - ZW171 is a bispecific antibody targeting mesothelin and CD3, designed to enhance T cell-mediated tumor cell killing, with promising preclinical data supporting its efficacy [15][34] - ZW191 is an antibody-drug conjugate targeting folate receptor-α, showing strong activity across various cancer models, including those with low levels of the target [16][17] Clinical Development - The company is actively recruiting for Phase 1 studies of ZW171 and ZW191, with plans for an investigational new drug application for ZW251 in mid-2025 [34] - Zymeworks has established partnerships with BeiGene and Jazz Pharmaceuticals for the development and commercialization of zanidatamab in different territories [33][34]

Core Viewpoint - Zymeworks Inc. is advancing its clinical-stage pipeline with the presentation of new preclinical data for ZW1528, a bispecific molecule targeting IL-4Rα and IL-33, aimed at treating respiratory inflammation, particularly chronic obstructive pulmonary disease (COPD) [1][2]. Group 1: Product Development - ZW1528 demonstrates high affinity binding to IL-4Rα and IL-33, effectively blocking IL-4, IL-13, and IL-33 signaling pathways, which are critical in respiratory inflammation [5][6]. - The bispecific design of ZW1528 shows promising manufacturability and stability, supporting high dosing concentrations and subcutaneous administration [5][7]. - Zymeworks is also developing ZW1572, another bispecific inhibitor targeting IL-4Rα and IL-31 for atopic dermatitis, as part of its expanding IL-4Rα program portfolio [3][5]. Group 2: Preclinical Data and Findings - Preclinical data presented at the ATS conference indicate that ZW1528 can suppress both Type 2 and non-Type 2 immune responses in primary human immune cells from COPD patients [6][7]. - In vivo studies in murine models of lung inflammation show efficacy for ZW1528, with extended pharmacokinetics observed in rodent and non-human primate models [6][7]. - The bispecific antibody's blockade of cytokine-driven activation in human epithelial cells is superior to that achieved with monoclonal antibodies targeting either IL-4Rα or IL-33 [7]. Group 3: Company Overview - Zymeworks is a global biotechnology company focused on developing multifunctional biotherapeutics for difficult-to-treat conditions, including cancer and autoimmune diseases [8]. - The company has a robust pipeline of product candidates and has entered into strategic partnerships to enhance its therapeutic platforms [8].

Core Viewpoint - Zymeworks Inc. (ZYME) shows significant potential for upside, with a mean price target of $21.35 indicating an 83.9% increase from the current price of $11.61 [1] Price Targets and Analyst Consensus - The average of 10 short-term price targets ranges from a low of $12 to a high of $30, with a standard deviation of $7.45, suggesting variability in analyst estimates [2] - The lowest estimate indicates a 3.4% increase, while the highest suggests a 158.4% upside [2] - A low standard deviation indicates strong agreement among analysts regarding the stock's price movement [9] Earnings Estimates and Analyst Optimism - Analysts show strong agreement in revising ZYME's earnings estimates higher, which correlates with potential stock price increases [11] - Over the last 30 days, the Zacks Consensus Estimate for the current year has increased by 1.6%, with two estimates moving higher and no negative revisions [12] - ZYME holds a Zacks Rank 2 (Buy), placing it in the top 20% of over 4,000 ranked stocks based on earnings estimates [13] Caution on Price Targets - Solely relying on price targets for investment decisions may not be wise, as analysts' ability to set unbiased targets has been questioned [3][7] - Analysts often set overly optimistic price targets due to business incentives, which can lead to inflated estimates [8] - While price targets should not be ignored, they should be approached with skepticism [10]

Company Performance - Zymeworks Inc. reported a quarterly loss of $0.30 per share, better than the Zacks Consensus Estimate of a loss of $0.45, and an improvement from a loss of $0.42 per share a year ago, resulting in an earnings surprise of 33.33% [1] - The company posted revenues of $27.11 million for the quarter ended March 2025, exceeding the Zacks Consensus Estimate by 57.36%, compared to revenues of $10.03 million in the same quarter last year [2] - Over the last four quarters, Zymeworks has surpassed consensus EPS estimates four times, but has only topped consensus revenue estimates once [2] Stock Outlook - Zymeworks shares have declined approximately 22.5% since the beginning of the year, while the S&P 500 has decreased by 4.3% [3] - The company's earnings outlook will be crucial for future stock performance, with current consensus EPS estimates at -$0.51 for the coming quarter and -$1.75 for the current fiscal year [4][7] Industry Context - The Medical - Biomedical and Genetics industry, to which Zymeworks belongs, is currently ranked in the top 33% of over 250 Zacks industries, indicating a favorable outlook compared to the bottom 50% [8] - Empirical research suggests a strong correlation between near-term stock movements and trends in earnings estimate revisions, which can impact Zymeworks' stock performance [5]

Financial Data and Key Metrics Changes - The company reported a net loss of $22.6 million for Q1 2025, a decrease from a net loss of $31.7 million in Q1 2024, primarily due to increased revenue [11] - Revenue for Q1 2025 was $27.1 million, significantly up from $10 million in Q1 2024, driven by milestone revenues and development support [11][12] - Operating expenses increased to $52.7 million in Q1 2025 from $47.3 million in Q1 2024, reflecting a 10% rise [12][13] Business Line Data and Key Metrics Changes - Milestone revenue included $14 million from GSK and $3.1 million from Daiichi Sankyo, contributing to the overall revenue growth [11] - Research and development expenses rose to $35.7 million in Q1 2025 from $32 million in Q1 2024, mainly due to increased costs associated with ZW251 and other preclinical research [12] Market Data and Key Metrics Changes - The company anticipates increased royalty revenue from the potential approval of zanadatumab for advanced HER2 positive biliary tract cancer, with a final decision expected soon [10] - The company is also looking forward to presenting data at several upcoming medical conferences, which may enhance its market presence [9] Company Strategy and Development Direction - The company emphasizes a disciplined approach to cash burn and pipeline management, focusing on evidence-based decisions tied to clinical validation [8] - The R&D strategy includes advancing a diverse pipeline of ADCs and T cell engagers, with a focus on unmet needs in oncology and immunology [36][40] - The company plans to submit an IND for ZW251 by mid-2025, marking a significant milestone in its development strategy [36] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in the company's ability to navigate the dynamic biotech environment while delivering shareholder value [7][8] - The company remains well-capitalized with $321.6 million in cash and equivalents, projected to fund operations into the second half of 2027 [14][38] - Management highlighted the importance of clinical progress and disciplined capital allocation in creating long-term shareholder value [40] Other Important Information - The company presented six posters at the AACR annual meeting, showcasing advancements in its R&D pipeline [16][35] - The recent appointment of Dr. Sabine McCann as Senior VP of Clinical Development is expected to enhance the company's clinical strategy [37] Q&A Session Summary Question: What are the base case assumptions regarding milestone royalty revenues? - Management emphasized the importance of capital allocation and expressed excitement about the progress made by partners Jazz and Beijing, which could impact future revenues [44][46] Question: Can you provide details on the cytokine induction data for ZW209? - The design of ZW209 allows for localized T cell activation, which may limit cytokine release syndrome, presenting a favorable safety profile compared to other approaches [50][52] Question: How do you view the impact of ex-US patients in the Horizon GEA trial? - Management noted that there is generally no significant difference in efficacy across ethnicities, but they are monitoring the data closely [58][60] Question: What is the expectation for the KLK2 bispecific update at ASCO? - Management indicated that they are looking forward to the data presentation and highlighted the financial interest in the partnership with J&J [63][64] Question: How many internal programs can the company support? - The company can handle approximately five internal programs through phase one and about ten preclinical programs at any one time [87]

Making a Meaningful Difference Accelerating the next generation of therapeutics to improve the standard of care for the most challenging diseases in cancer, autoimmune and inflammatory disease May 2025 Nasdaq: ZYME | zymeworks.com The above assumptions, risks and uncertainties are not exhaustive. Forward-looking statements are made as of the date hereof and, except as may be required by law, Zymeworks undertakes no obligation to update, republish, or revise any forward-looking statements to reflect new info ...

Financial Performance - Total revenue for the three months ended March 31, 2025, was $27,110,000, a significant increase from $10,030,000 in the same period of 2024, representing a 170% growth[21] - The net loss for the three months ended March 31, 2025, was $22,636,000, an improvement from a net loss of $31,653,000 in Q1 2024, indicating a reduction of 28%[21] - The company reported a comprehensive loss of $22,090,000 for Q1 2025, compared to a comprehensive loss of $32,774,000 in Q1 2024, reflecting a 33% improvement[21] - Basic net loss per share improved to $(0.30) in Q1 2025 from $(0.42) in Q1 2024[35] - The net loss for Q1 2025 was $22,636,000, a 28.5% improvement from a net loss of $31,653,000 in Q1 2024[23] Research and Development - Research and development expenses for Q1 2025 were $35,738,000, compared to $32,042,000 in Q1 2024, reflecting an increase of 23%[21] - The company continues to focus on research and development of next-generation multifunctional biotherapeutics[25] - The company anticipates continued losses as it increases research and development expenditures for ongoing product candidate development[91] - Research and development expenses increased by 12% to $35.7 million for the three months ended March 31, 2025, compared to $32.0 million in the same period in 2024[132] - Research and development expenses for zanidatamab decreased by 59% to $1.4 million in Q1 2025 compared to $3.4 million in Q1 2024[132] Cash and Liquidity - Cash and cash equivalents increased to $76,204,000 as of March 31, 2025, compared to $66,103,000 at December 31, 2024, showing a growth of 15%[20] - The company has a cash resource of $321.6 million as of March 31, 2025, which is expected to fund operations for at least the next twelve months[90] - The company’s liquidity sources include cash, cash equivalents, and investments, which are deemed sufficient to fund operations for at least the next 12 months[75] - Cash used in operating activities decreased significantly to $3,407,000 in Q1 2025 from $37,675,000 in Q1 2024[23] - As of March 31, 2025, the company had $321.6 million in cash, cash equivalents, and marketable securities, including $76.2 million in cash and cash equivalents and $245.4 million in marketable securities[139] Assets and Liabilities - Total assets decreased to $425,522,000 as of March 31, 2025, down from $463,091,000 at the end of 2024, a decline of 8%[20] - Total current liabilities decreased to $65,103,000 as of March 31, 2025, down from $88,294,000 at December 31, 2024, a reduction of 26%[20] - The total stockholders' equity as of March 31, 2025, was $324,967,000, a decrease from $338,768,000 at the end of 2024, representing a decline of 4%[20] - The total liabilities decreased from $59,838 million as of December 31, 2024, to $38,223 million as of March 31, 2025[40] Strategic Partnerships and Revenue - The company recognized $27,110 in revenue from strategic partnerships in the three months ended March 31, 2025, compared to $10,030 in the same period of 2024, representing a 170% increase[59] - The company received $471.0 million in non-refundable upfront and milestone payments through collaboration agreements with Jazz and BeiGene, with potential future payments of up to $1.53 billion[113] - The company recognized $14.0 million in milestone revenue from GSK in January 2025, with potential future milestone payments totaling up to $203.5 million in R&D and $867.0 million in commercial payments[109] - The company received $3.1 million in milestone revenue from Daiichi Sankyo following the first patient dosed in a clinical trial, with potential future milestone payments totaling up to $60.3 million in development and $170.0 million in commercial payments[110] Clinical Development and Regulatory Approvals - The FDA granted accelerated approval for Ziihera® (zanidatamab-hrii) for the treatment of adults with previously-treated, unresectable or metastatic HER2-positive biliary tract cancer in 2024[86] - The company is currently focused on the development of two clinical-stage product candidates, ZW171 and ZW191, and is recruiting patients for ongoing global Phase 1 studies in multiple regions[173] - The confirmatory trial for Ziihera® related to its accelerated approval must demonstrate clinical benefit; failure could result in removal from the market, impacting milestone payments and royalties[172] - The FDA granted Fast Track and Breakthrough Therapy designations for zanidatamab, but these designations do not guarantee faster development or approval processes[190][191] Risks and Challenges - The company has incurred significant losses since inception and anticipates continued losses for the foreseeable future, requiring substantial additional funding that may not be available on acceptable terms[163] - Clinical trials are expensive and time-consuming, with high attrition rates; the company may face significant delays or inability to develop product candidates due to various factors[165][176] - Regulatory approval for product candidates is uncertain and may be impacted by changes in regulatory policies or disagreements with regulatory authorities regarding trial designs and data[169][177] - The company faces significant competition, and if competitors develop more effective or less expensive products, it could negatively impact commercial opportunities[162] - The company may encounter challenges in enrolling patients for clinical trials, particularly for rare diseases, which could hinder marketing approval[182]