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Palo Alto |
3175 Hanover Street |
Palo Alto, CA 94304-1130 |
Attention: Marya Postner |
Facsimile: +1 650 849 7400 |
13.9 Entire Agreement; Amendments. This Agreement, together with the Schedules attached hereto, sets forth and constitutes the entire agreement and understanding between the Parties with respect to the subject matter hereof and all prior agreements, understandings, promises, and representations, whether written or oral... |
13.10 English Language. This Agreement shall be written and executed in, and all other communications under or in connection with this Agreement shall be in, the English language. Any translation into any other language shall not be an official version thereof, and in the event of any conflict in interpretation between... |
13.11 Equitable Relief. Each Party acknowledges and agrees that the restrictions set forth in Section 5.7 and ARTICLE 7 and ARTICLE 9 are reasonable and necessary to protect the legitimate interests of the other Party and that such other Party would not have entered into this Agreement in the absence of such restrictio... |
13.12 Waiver and Non-Exclusion of Remedies. Any term or condition of this Agreement may be waived at any time by the Party that is entitled to the benefit thereof, but no such waiver shall be effective unless set forth in a written instrument duly executed by or on behalf of the Party waiving such term or condition. Th... |
13.13 No Benefit to Third Parties. Except as provided in ARTICLE 11, covenants and agreements set forth in this Agreement are for the sole benefit of the Parties hereto and their successors and permitted assigns, and they shall not be construed as conferring any rights on any other Persons. |
13.14 Further Assurance. Each Party shall duly execute and deliver, or cause to be duly executed and delivered, such further instruments and do and cause to be done such further acts and things, including the filing of such assignments, agreements, documents, and instruments, as may be necessary or as the other Party m... |
13.15 Relationship of the Parties. It is expressly agreed that Licensor, on the one hand, and AbbVie, on the other hand, shall be independent contractors and that the relationship between the Parties shall not constitute a partnership, joint venture, or agency, including for all tax purposes. Neither Licensor, on the o... |
13.16 Performance by Affiliates. AbbVie may use one (1) or more of its Affiliates to perform its obligations and duties hereunder and such AbbVie Affiliates are expressly granted certain rights herein; provided that each such Affiliate shall be bound by the corresponding obligations of AbbVie and, subject to an assignm... |
13.17 Counterparts; Facsimile Execution. This Agreement may be executed in two (2) counterparts, each of which shall be deemed an original, but all of which together shall constitute one (1) and the same instrument. This Agreement may be executed by facsimile or electronically transmitted signatures and such signatures... |
13.18 References. Unless otherwise specified, (a) references in this Agreement to any Article, Section or Schedule shall mean references to such Article, Section or Schedule of this Agreement, (b) references in any Section to any clause are references to such clause of such Section, and (c) references to any agreement,... |
13.19 Schedules. In the event of any inconsistencies between this Agreement and any schedules or other attachments hereto, the terms of this Agreement shall control. |
13.20 Construction. Except where the context otherwise requires, wherever used, the singular shall include the plural, the plural the singular, the use of any gender shall be applicable to all genders and the word "or" is used in the inclusive sense (and/or). Whenever this Agreement refers to a number of days, unless o... |
[SIGNATURE PAGE FOLLOWS.] |
Schedule 1.63 |
Humanized 5H10 Antibody |
VK3 Light Chain |
DVVMTQSPLSLPVTLGQPASISCKSSQSLLESDGKTYLNWLQQRPGQSPRRLIYLVSRLDSGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCWQGTHLPQTFGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC |
VH1 Heavy Chain |
QVQLVQSGAELKKPGSSVKISCKSSGYAFSSYWMNWVKQRPGQGLEWIGQIYPGDGDTHYNGKFKGKATLTADKSTSTAYMELSSLTSEDSAVYFCSSSNWVGSYWGQGTLVTVSSASTKGPSVFPLAPCRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPEFEGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSN... |
IgG4 Heavy chain constant region |
Kappa chain constant region |
S241P = hinge stabilising |
L248E= reduces effector function |
(Kabat numbering) |
Schedule 1.72 |
Initial Development Plan and Budget |
Attached. |
Project Onyx |
Initial Development Plan and Budget |
AbbVie contributors/principal owners: |
Function Key owner supported by S&E (GNG) |
Clinical Ana Lacerda, Maureen Kelly |
Translational Science Thierry Sornasse |
CPPM Hoi Kei Lon |
PPM Hedley Stickell |
CPD Rita Wozniak |
Development Sciences Kennan Marsh, David Honor |
CMC Biologics John Morris, Alane Wentz, Hans-Juergen Krause |
Regulatory Lee Muraoka |
Statistics Zailong Wang |
PPS Dilek Arikan |
Table of Contents |
I. Introduction.................................................................................................................... 3 |
A. Plan Rationale and Goals ........................................................................................... 3 |
II. Elements of Readiness Plan ......................................................................................... 6 |
A. Quality Plan............................................................................................................... 7 |
B. Project Management .................................................................................................. 7 |
III. Initial Research and Development Plans....................................................................10 |
A. Readiness and Operational Plan and Budget ..............................................................10 |
B. Clinical Plan .............................................................................................................10 |
C. Initial Phase I/IA Trial IV/SC formulation PK Studies ...............................................18 |
D. Phase I/IA Trial IV/SC Formulation PK Bridging Studies ..........................................18 |
E. Initial CMC Development Plan Activities .....................................................................19 |
IV. Pre-Clinical Activities.................................................................................................35 |
A. cGLP Toxicology .....................................................................................................35 |
B. Clinical Assay Development .....................................................................................36 |
C. Other Preclinical Activities .......................................................................................39 |
D. Regulatory Affairs ....................................................................................................39 |
V. Program Target Success Criteria ...............................................................................41 |
A. Success Criteria for IND ...........................................................................................41 |
B. Success Criterias for End of Phase I/IA Trial .............................................................42 |
C. Success Criterias for End of PoC Phase I/IB Trial ......................................................43 |
VI. Data Package Delivery Requirements ........................................................................44 |
A. Clinical.....................................................................................................................44 |
B. Nonclinical and Bioanalytical....................................................................................46 |
C. CMC Development Reports (Cell line, Formulation, Process) ....................................46 |
D. Analytical Reports ....................................................................................................47 |
VII. Budget Summary........................................................................................................48 |
I. Introduction |
A. Plan Rationale and Goals |
1. Development to Proof of Concept (PoC) Phase I/IB Trial Plan |
The operational objective of this Initial Development Plan and Budget is to develop a subcutaneous (SC) formulation of a Licensed Antibody, execute a first-in-human Single Ascending Dose and Multiple Ascending Dose (SAD/MAD) Phase I/IA Trial in healthy volunteers (HV), and demonstrate proof of concept (PoC), preliminar... |
2. Preclinical R&D |
In parallel to the critical path activities of cGMP manufacturing to support (IND-enabling) cGLP toxicology studies, Opsidio and its subcontractors will be continuing preclinical activities to support the clinical development of the Licensed Antibodies. These include the development of non-standard PD markers, the gene... |
Several non-standard PD markers will be required in the Clinical Studies. These include optimization of standard laboratory techniques, such as flow cytometry to detect c-kit-positive cells. Also, there will be a number of non-standard tests that need to be developed to measure biomarkers of disease, such as tissue cyt... |
In approximately March, 2021 the sequence patent for the Humanized 5H10 Antibody will be published, which includes the sequence of the the Humanized 5H10 Antibody and sequences adjacent to the Humanized 5H10 Antibody. |
Specifically, Opsidio will generate additional Licensed Antibodies, including through the CMC activities described below, which Opsidio will characterize. Any sequences that prove useful will be patented before the publication of the Humanized 5H10 Antibody sequence patent. Similarly, Specifica will generate sequences ... |
3. IND-enabling activities to Phase I/IA and Phase I/IB Trials |
• The key steps are the timing of transfection and generation of a commercially viable stable cell line from Selexis to KBI Biopharma to initiate manufacturing, and the timely completion of the 13-week toxicology study |
• Commercially viable process and SC formulation |
• Clinical drug supply |
• SAD/MAD Phase I/IA Trial clinical protocol |
• PoC Phase I/IB Trial clinical protocol in adult subjects with moderate to severe AD |
• Selection of Phase I/IA unit(s)/central lab with capabilities for flow cytometry |
• CRO selection 6 months prior to study initiation |
• PD marker assay implementation |
4. IND preparation/submission |
The timing of the availability of a Licensed Antibody for toxicology studies is the main driver of the IND timeline. The key steps are the generation of a commercially viable stable cell line from Selexis to KBI Biopharma to initiate manufacturing, and the timely completion of the 13-week toxicology study, with a draft... |
The pre-IND package will include a concise pharmacologic rationale, a description of the CMC and cGLP toxicology programs, and detailed protocol synopsis of the SAD/MAD Phase I/IA Trial in HV and the PoC Phase I/IB Trial in AD subjects, including a description of the planned PD markers in the usual question format. The... |
The IND will be submitted in eCTD format. The CMC (product quality) section and overview (i.e. Quality Overall Summary) will be prepared by BPTG, BDO USA, and the toxicology reports and overviews (i.e. Written and Tabulated Summaries) will be provided by Charles River Laboratories. Opsidio will prepare the pharmacology... |
Major Activities |
1. Clinical protocol development for the SAD/MAD Phase I/IA Trial in HV and PoC Phase I/IB Trial in AD subjects |
2. Write sections of pIND and IND |
3. Pre-IND meeting |
a. Prepare and schedule |
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