Contract analysis

I. EXECUTIVE SUMMARY A. Purpose This memorandum summarizes the findings of the intellectual property due diligence review conducted by Calderwood & Harkness LLP ("C&H" or "we") in connection with the Special Committee's evaluation of the proposed acquisition by Penterra Pharmaceuticals Corp. ("Penterra" or the "Buyer") of one hundred percent (100%) of the outstanding equity of Caliston BioSciences, Inc. ("Caliston" o

1. Patent Portfolio. Review and analysis of all issued patents and pending patent applications owned by or licensed to Caliston, including composition of matter, methods of use, formulation, process, and related patent families across all relevant jurisdictions (United States, European Patent Office, Patent Cooperation Treaty applications, and major commercial markets including Japan, China, Canada, Australia, and So

2. Trade Secrets and Know-How. Assessment of Caliston's trade secret protection policies, procedures, and practices, including confidentiality and non-disclosure agreements, information security measures, and proprietary manufacturing processes, clinical data, and compound libraries.

3. Trademarks and Domain Names. Review of registered and pending trademarks and internet domain name registrations.

4. IP Assignment Chain. Tracing the chain of title for all material intellectual property from the original inventors (including the founders) through to Caliston, including employee and consultant assignment agreements.

5. Freedom-to-Operate Analyses. Review and assessment of Caliston's internal and externally commissioned freedom-to-operate ("FTO") analyses for CLT-4019 and, to the extent available, for the preclinical candidates.

6. License Agreements. Review and analysis of all in-license, out-license, collaboration, and research agreements that include intellectual property ownership, licensing, or encumbrance provisions.

7. Third-Party Infringement Risks. Identification and assessment of potential third-party patent infringement risks, including competitive landscape analysis in the CDK4/6 inhibitor space. Our review addressed the intellectual property related to the following Caliston product candidates and programs: • CLT-4019 — A selective cyclin-dependent kinase 4/6 ("CDK4/6") inhibitor being developed for the treatment of hormon

1. Partial Assignment Chain Gap. We identified two former employees (out of nineteen former employees involved in R&D activities) for whom executed Proprietary Information and Inventions Assignment Agreements ("PIIAs") were not located in the data room. Although neither individual is a named inventor on any Caliston patent or application, one individual (Dr. Leila Farooq, former Senior Research Scientist, employed Ja

2. Third-Party FTO Risk — Vantara Therapeutics Patent Family. The Meridian FTO analysis identified one patent family owned by Vantara Therapeutics, Inc. ("Vantara") (U.S. Patent No. 10,611,742 and related family members) as posing a medium risk to CLT-4019. While Caliston's outside patent counsel has opined that CLT-4019 does not infringe the asserted claims under their best reading, the breadth of certain Markush cl

3. Change-of-Control Provision in Westlake University License Agreement. The exclusive license agreement between Westlake University and Caliston (the "Westlake License"), which covers certain foundational platform technology patents underlying the Company's kinase inhibitor screening methodology, contains a change-of-control provision requiring thirty (30) days' prior written notice to Westlake and Westlake's consen

4. Early-Stage Pipeline IP Uncertainty. The patent portfolios for CLT-5227 and CLT-6034 are at an early stage (provisional applications only for CLT-6034), and the ultimate scope of patent protection for these candidates remains uncertain. Recommendation. Notwithstanding the foregoing concerns, which we believe are manageable through appropriate Transaction structuring and contractual protections, we do not believe t

II. IP ASSIGNMENT CHAIN — FOUNDERS TO CALISTON A. Founder Assignment Agreements Caliston was founded in 2017 by Dr. Nadia Sorensen and Dr. Raj Malhotra. Dr. Sorensen currently serves as Chief Executive Officer and holds approximately 14.2% of the outstanding equity of the Company. Dr. Malhotra currently serves as Chief Scientific Officer and holds approximately 9.8% of the outstanding equity. Together, the founders h

1. Invention Assignment and Confidential Information Agreement between Caliston BioSciences, Inc. and Dr. Nadia Sorensen, dated September 12, 2017 (the "Sorensen Assignment Agreement"). This agreement provides for the irrevocable, perpetual, and worldwide assignment to the Company of all of Dr. Sorensen's right, title, and interest in and to all inventions, discoveries, improvements, works of authorship, trade secret

2. Invention Assignment and Confidential Information Agreement between Caliston BioSciences, Inc. and Dr. Raj Malhotra, dated September 12, 2017 (the "Malhotra Assignment Agreement" and, together with the Sorensen Assignment Agreement, the "Founder Assignments"). This agreement contains substantively identical terms to the Sorensen Assignment Agreement, providing for the irrevocable, perpetual, and worldwide assignme

1. Employee PIIAs Caliston utilizes a standard form Proprietary Information and Inventions Assignment Agreement ("PIIA") for all of its employees. We reviewed the current form of the PIIA (rev. March 2019) and confirmed that it contains the following provisions: • Assignment of all inventions, discoveries, improvements, works of authorship, trade secrets, and other intellectual property conceived, developed, or reduc

2. Treatment of Dr. Evan Whitmore We specifically reviewed the employment records and PIIA for Dr. Evan Whitmore, Caliston's Head of Clinical Development and a member of the Caliston Board of Directors. Dr. Whitmore's situation warrants particular attention because his spouse, Angela Whitmore, serves on the Board of Directors of Penterra, which is among the reasons the Special Committee was constituted to evaluate th

3. Consultant and Contractor IP Assignments Caliston engages a number of scientific advisors, consultants, and contract research organizations ("CROs") in connection with its research and clinical development programs. We reviewed the IP assignment and ownership provisions in the following categories of agreements: • Scientific Advisory Board Agreements. Caliston's Scientific Advisory Board currently comprises seven

1. Bayh-Dole Act Analysis We analyzed whether any Caliston intellectual property originated from or was derived from research funded by the United States federal government, which would implicate the Bayh-Dole Act (35 U.S.C. §§ 200–212) and potentially subject the intellectual property to federal government rights, including march-in rights. Dr. Sorensen's prior research at Marfield University was funded in part by g

2. University License-In Agreements As described in greater detail in Section VI.A below, Caliston holds an exclusive license from Westlake University (the "Westlake License") covering certain foundational platform technology patents related to kinase inhibitor screening methodology. These patents (U.S. Patent Nos. 9,845,271 and 10,202,394, along with corresponding foreign family members) were developed at Westlake's

III. CLT-4019 PATENT PORTFOLIO ANALYSIS A. Overview of CLT-4019 CLT-4019 is a selective CDK4/6 inhibitor being developed for the treatment of HR+/HER2– metastatic breast cancer. CLT-4019 is designed to offer an improved selectivity profile relative to existing approved CDK4/6 inhibitors (palbociclib, ribociclib, and abemaciclib), potentially resulting in reduced hematologic toxicity while maintaining or improving eff

1. U.S. Patent No. 10,842,776 — "Methods of Treating HR+/HER2– Breast Cancer with Substituted Pyridopyrimidinone CDK4/6 Inhibitors." Filed January 22, 2019; priority date October 20, 2017. Issued November 24, 2020. Claims directed to methods of treating HR+/HER2– metastatic breast cancer by administering a therapeutically effective amount of CLT-4019 to a patient in need thereof. Additional claims cover specific dosi

2. U.S. Application No. 17/458,291 — "Combination Therapy with CLT-4019 and Endocrine Agents." Filed August 26, 2021. Pending. Claims directed to methods of treating HR+/HER2– metastatic breast cancer using CLT-4019 in combination with specific endocrine therapy agents, including methods for patients who have progressed on prior CDK4/6 inhibitor therapy. This is the application on which Dr. Evan Whitmore is a named i

3. EP Application No. 19 703 482.6 — Methods of use claims corresponding to U.S. 10,842,776, currently pending before the EPO. Examination is ongoing; a communication under Article 94(3) EPC was received in February 2023. Assessment. The methods of use patents and applications provide an additional layer of protection for CLT-4019, complementing the composition of matter portfolio. Methods of use patents are particul

1. U.S. Application No. 17/122,844 — "Pharmaceutical Formulations Comprising Substituted Pyridopyrimidinone CDK4/6 Inhibitors." Filed December 15, 2020. Pending. Claims directed to oral dosage forms (tablets and capsules), including specific excipient compositions, dissolution profiles, and stability characteristics. A non-final office action was received on October 3, 2022, and a response was filed on January 3, 202

2. U.S. Application No. 17/389,207 — "Polymorphic Forms of CLT-4019 and Processes for Preparation Thereof." Filed July 29, 2021. Pending. Claims directed to specific crystalline polymorphs (Form I and Form II) of CLT-4019, characterized by X-ray powder diffraction patterns, differential scanning calorimetry data, and infrared spectroscopy data, and processes for their preparation. This application is at an early stag

3. PCT/US2022/038471 — "Processes for Large-Scale Manufacture of Substituted Pyridopyrimidinone Compounds." Filed July 27, 2022. Currently in the international phase; national phase entries are expected to be filed in the first quarter of 2024 in the United States, Europe, Japan, China, and other key markets. Assessment. The formulation and process patent applications, if granted, will provide important supplemental

IV. FREEDOM-TO-OPERATE ANALYSIS — CLT-4019 A. Landscape Assessment We reviewed Caliston's internal FTO analysis, which was prepared by Meridian Patent Analytics LLC ("Meridian") under the direction of Caliston's outside patent prosecution counsel, Brookhaven IP Group LLP ("Brookhaven"), and is dated September 15, 2022 (the "Meridian FTO Report"). The Meridian FTO Report analyzed the third-party patent landscape as of

1. Vantara Therapeutics Patent Family (Medium Risk) Patent Family: U.S. Patent No. 10,611,742 ("Heterocyclic Compounds as Kinase Inhibitors"); corresponding family members EP 3,412,668 B1 (granted, validated in DE, FR, GB), JP 7,052,881 (granted), and WO 2017/162873 (PCT). Owner: Vantara Therapeutics, Inc. (San Diego, CA), a privately held clinical-stage biopharmaceutical company developing kinase inhibitors for onco

2. Arisawa Chemical Industries Patent Family (Medium Risk) Patent Family: U.S. Application No. 16/989,773 (pending, published as US 2021/0047298 A1); corresponding PCT Application WO 2021/024107. Owner: Hollowell Industries (Osaka, Japan), a diversified chemical company with a pharmaceutical intermediates division. Relevant Claims: The published claims are directed to intermediate compounds and processes for their pr

3. Other Identified Families (Low Risk) The remaining twelve (12) families classified by Meridian as low risk involve patents and applications owned by major pharmaceutical companies and academic institutions covering various aspects of CDK4/6 inhibition, kinase inhibitor formulations, and combination therapy methods. In each case, we concur with Meridian's assessment that the claims are unlikely to cover CLT-4019 ba

4. Litigation History We confirmed with Caliston management and through a review of the legal due diligence report prepared by C&H's Litigation Due Diligence team that Caliston has not received any cease-and-desist letters, demand letters, or threats of patent infringement litigation from any third party as of the date of this memorandum. Caliston is not a party to any pending or threatened IP litigation. No third-pa

1. Structural Design-Around (Vantara Family). CLT-4019 is a specific compound that has been the subject of extensive clinical development and cannot be structurally modified without restarting the clinical program. Accordingly, a structural design-around for CLT-4019 itself is not feasible. However, for future analogs and next-generation compounds (including potential follow-on candidates from the CLT-4019 series), C

2. Process Design-Around (Arisawa Family). If the Arisawa claims are granted in their current form, Caliston's process chemistry team has identified at least two alternative synthetic routes for CLT-4019 that do not employ the intermediate claimed in the Arisawa application. These alternative routes would require process development and validation but are technically feasible and could be implemented within approxima

3. Licensing. We recommend exploring the availability of licenses from both Vantara and Arisawa as a potential cost-effective mitigation strategy, particularly given that neither party's core business directly competes with CLT-4019's target indication.

4. Invalidity Defenses. As noted above, strong invalidity arguments are available against the Vantara patent (lack of written description and enablement for the full Markush genus; anticipation and obviousness based on prior art) and potentially against the Arisawa application (anticipation based on Caliston's own publications). These defenses could be asserted in litigation or in IPR proceedings.

V. PRECLINICAL CANDIDATES — CLT-5227 AND CLT-6034 A. CLT-5227 CLT-5227 is a preclinical-stage kinase inhibitor candidate targeting a distinct kinase target (identity withheld at Caliston's request; designated internally as "Target X"). CLT-5227 is currently in lead optimization and early IND-enabling studies. Caliston anticipates filing an IND for CLT-5227 in the second half of 2024. Patent Portfolio. Caliston has fi

VI. KEY LICENSE AGREEMENTS A. In-License Agreements We identified two license agreements under which Caliston is a licensee of third-party intellectual property:

1. Westlake University Exclusive License Agreement Parties: Westlake University ("Westlake" or "Licensor") and Caliston BioSciences, Inc. ("Licensee") Date: January 15, 2018 (as amended by First Amendment dated March 22, 2020) Licensed Technology: U.S. Patent No. 9,845,271, U.S. Patent No. 10,202,394, and corresponding foreign family members (EP, JP, CN), directed to methods and compositions for high-throughput scree