An Open-Label, Multicenter Evaluation of the Long-Term Safety and Efficacy of Recombinant Human Coagulation Factor VIII Fusion Protein (rFVIIIFc) in the Prevention and Treatment of Bleeding Episodes in Previously Treated Subjects With Hemophilia A - ASPIRE
2015-07-05·International Journal of Pharmaceutics (Amsterdam, Netherlands)2区 · 医学
Development of a NIR-based blend uniformity method for a drug product containing multiple structurally similar actives by using the quality by design principles
2区 · 医学
作者: Lin, Yiqing ; Li, Weiyong ; Xu, Jin ; Boulas, Pierre
The aim of this study is to develop an at-line near infrared (NIR) method for the rapid and simultaneous determination of four structurally similar active pharmaceutical ingredients (APIs) in powder blends intended for the manufacturing of tablets. Two of the four APIs in the formula are present in relatively small amounts, one at 0.95% and the other at 0.57%. Such small amounts in addition to the similarity in structures add significant complexity to the blend uniformity analysis. The NIR method is developed using spectra from six laboratory-created calibration samples augmented by a small set of spectra from a large-scale blending sample. Applying the quality by design (QbD) principles, the calibration design included concentration variations of the four APIs and a main excipient, microcrystalline cellulose. A bench-top FT-NIR instrument was used to acquire the spectra. The obtained NIR spectra were analyzed by applying principal component analysis (PCA) before calibration model development. Score patterns from the PCA were analyzed to reveal relationship between latent variables and concentration variations of the APIs. In calibration model development, both PLS-1 and PLS-2 models were created and evaluated for their effectiveness in predicting API concentrations in the blending samples. The final NIR method shows satisfactory specificity and accuracy.
2015-05-01·Thrombosis Research3区 · 医学
Enhanced Pharmacokinetics of Factor VIIa as a Monomeric Fc Fusion
3区 · 医学
作者: Salas, Joe ; Liu, Tongyao ; Lu, Qi ; Kulman, John D. ; Ashworth, Tamera ; Kistanova, Elena ; Moore, Nancy ; Pierce, Glenn F. ; Jiang, Haiyan ; Peters, Robert
Recombinant Factor VIIa (rFVIIa) is utilized for on-demand treatment of bleeding episodes in hemophilia patients with neutralizing antibodies (inhibitors) against Factor VIII or Factor IX, but a short half-life in the circulation (~2.5hrs) limits its use in a prophylactic setting. Recombinant FVIIa variants with improved pharmacokinetic properties may enable improved treatment and prevention of bleeding episodes in the inhibitor population. In this study we describe recombinant FVIIaFc (rFVIIaFc), a recombinant Fc-fusion protein generated to utilize the neonatal Fc receptor (FcRn)-mediated recycling pathway that protects immunoglobulin G from catabolism. On the basis of activity, rFVIIaFc exhibited a 5.5-fold extension in terminal half-life in hemophilia A mice compared to rFVIIa. The potency of rFVIIaFc was comparable to that of rFVIIa in thrombin generation assay and ROTEM. In agreement with these data, rFVIIaFc and rFVIIa showed similar acute efficacy at comparable molar doses in the tail clip bleeding model in hemophilia A mice. Taken together, these studies demonstrate enhanced pharmacokinetics and similar hemostatic properties for rFVIIaFc compared to rFVIIa.
2015-04-06·Molecular Pharmaceutics2区 · 医学
Examination of Thermal Unfolding and Aggregation Profiles of a Series of Developable Therapeutic Monoclonal Antibodies
2区 · 医学
作者: Brader, Mark L. ; Estey, Tia ; Bai, Shujun ; Alston, Roy W. ; Lucas, Karin K. ; Lantz, Steven ; Landsman, Pavel ; Maloney, Kevin M.
Screening for pharmaceutically viable stability from measurements of thermally induced protein unfolding and short-term accelerated stress underpins much molecule design, selection, and formulation in the pharmaceutical biotechnology industry. However, the interrelationships among intrinsic protein conformational stability, thermal denaturation, and pharmaceutical stability are complex. There are few publications in which predictions from thermal unfolding-based screening methods are examined together with pharmaceutically relevant long-term storage stability performance. We have studied eight developable therapeutic IgG molecules under solution conditions optimized for large-scale commercial production and delivery. Thermal unfolding profiles were characterized by differential scanning calorimetry (DSC) and intrinsic fluorescence recorded simultaneously with static light scattering (SLS). These molecules exhibit a variety of thermal unfolding profiles under common reference buffer conditions and under individually optimized formulation conditions. Aggregation profiles by SE-HPLC and bioactivity upon long-term storage at 5, 25, and 40 °C establish that IgG molecules possessing a relatively wide range of conformational stabilities and thermal unfolding profiles can be formulated to achieve pharmaceutically stable drug products. Our data suggest that a formulation design strategy that increases the thermal unfolding temperature of the Fab transition may be a better general approach to improving pharmaceutical storage stability than one focused on increasing Tonset or Tm of the first unfolding transition.
BOSTON, July 26, 2023 (GLOBE NEWSWIRE) -- Monte Rosa Therapeutics, Inc. (NASDAQ: GLUE), a clinical stage biotechnology company developing novel molecular glue degrader (MGD)-based medicines, today announced the appointment of Anthony M. Manning, Ph.D., to its Board of Directors. Dr. Manning is a highly accomplished drug discovery leader in the field of autoimmune and inflammatory diseases. ”Dr. Manning brings extensive knowledge and experience in the field of immunology and inflammation to our Board of Directors, and we’re delighted to have him on our team,” said Markus Warmuth, M.D., CEO of Monte Rosa. ”Tony’s experience developing multiple first-in-class therapeutics for the treatment of immune-driven diseases will be invaluable, particularly as our VAV1 program for autoimmune diseases approaches the clinic, followed closely by our NEK7 program for inflammatory diseases. We are proud to pioneer the development of MGDs beyond oncology and in particular, in the areas of immune and inflammatory conditions. With the team we’ve assembled and leveraging the power of our QuEEN™ platform to discover highly selective MGDs of key drivers of a variety of crucial immune cell pathways, we are confident we can help a broad group of patients with high unmet medical needs.” Dr. Manning serves as a Board Director for Palatin Technologies, Founder and Chair of the non-profit Institute for Biomedical Entrepreneurship, and Scientific Advisor for several companies. Most recently, Dr. Manning was Chief Scientific Officer at Momenta Pharmaceuticals, where he built a pipeline of first-in-class therapeutics for the treatment of autoantibody-driven diseases. Momenta was acquired by Johnson & Johnson Corporation in 2020 for $6.5 billion. Prior to Momenta, Dr. Manning led research and drug discovery efforts at Roche Pharmaceuticals, Pharmacia Corp., Biogen Idec, and several early-stage biotechnology companies. Dr. Manning has contributed more than 120 scientific publications and patents in the fields of autoimmune diseases, novel therapeutics, and drug discovery. “The ability to eliminate immune targets previously considered undruggable, like VAV1, affords Monte Rosa an incredible advantage, particularly when you consider the incredible specificity of degradation demonstrated by their preclinical data,” said Dr. Manning. “I am excited to support Monte Rosa Therapeutics on its path to become the first company to progress the concept of molecular glue-based protein degradation into the immunology and inflammation field, and think the team and company are uniquely positioned to do so. I look forward to working with the Board and leadership team as they advance the company’s pipeline and bring differentiated and transformational MGD-based therapies to patients.” About Monte RosaMonte Rosa Therapeutics is a biotechnology company developing novel molecular glue degrader (MGD) medicines for patients with serious diseases such as oncology, autoimmune, and inflammatory diseases. MGDs are small molecule protein degraders that employ the body’s natural mechanisms to selectively eliminate therapeutically relevant proteins. The company’s QuEEN™ (Quantitative and Engineered Elimination of Neosubstrates) platform enables it to rapidly identify protein targets and design highly selective degraders by combining diverse libraries of proprietary MGDs with in-house proteomics, structural biology, AI/machine learning, and computational chemistry capabilities. For more information, visit www.monterosatx.com. Forward-Looking StatementsThis communication includes express and implied “forward-looking statements,” including forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Forward looking statements include all statements that are not historical facts, and in some cases, can be identified by terms such as “may,” “might,” “will,” “could,” “would,” “should,” “expect,” “intend,” “plan,” “objective,” “anticipate,” “believe,” “estimate,” “predict,” “potential,” “continue,” “ongoing,” or the negative of these terms, or other comparable terminology intended to identify statements about the future. Forward-looking statements contained herein include, but are not limited to, statements about our product development activities, including expectations around the advancement of our pipeline and the various products therein, their therapeutic potential and the anticipated contribution of the members of our board of directors, specifically Dr. Manning, and our executives to our operations and progress. By their nature, these statements are subject to numerous risks and uncertainties, including those risks and uncertainties set forth in our most recent Annual Report on Form 10-K for the year ended December 31, 2022 filed with the US Securities and Exchange Commission, and any subsequent filings, that could cause actual results, performance or achievement to differ materially and adversely from those anticipated or implied in the statements. You should not rely upon forward looking statements as predictions of future events. Although our management believes that the expectations reflected in our statements are reasonable, we cannot guarantee that the future results, performance or events and circumstances described in the forward-looking statements will be achieved or occur. Recipients are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date such statements are made and should not be construed as statements of fact. We undertake no obligation to publicly update any forward-looking statements, whether as a result of new information, any future presentations or otherwise, except as required by applicable law. ContactsInvestorsShai Biran Monte Rosa Therapeutics email@example.com MediaCory Tromblee Scient Public Relationsmedia@monterosatx.com
"Global Clinical Stage Partnering Terms and Agreements in Pharma and Biotech 2016-2023"
report has been added to
The Global Clinical Stage Partnering Terms and Agreements in Pharma and Biotech 2016 - 2023 report provides comprehensive access to available deals and contract documents for over 2,900 clinical stage deals.
The report provides a detailed understanding and analysis of how and why companies enter clinical stage partnering deals and provides details of the latest clinical agreements announced in the healthcare sector.
Understanding the flexibility of a prospective partner's negotiated deals terms provides critical insight into the negotiation process in terms of what you can expect to achieve during the negotiation of terms. Whilst many smaller companies will be seeking details of the payments clauses, the devil is in the detail in terms of how payments are triggered - contract documents provide this insight where press releases and databases do not.
This report contains a comprehensive listing of over 2,900 clinical stage partnering deals announced since 2016 including financial terms where available including numerous links to online deal records of actual clinical partnering deals as disclosed by the deal parties. In addition, where available, records include contract documents as submitted to the Securities Exchange Commission by companies and their partners.
The report includes deals announced by hundreds of life science companies including big pharma such as Abbott, Abbvie, Actavis, Amgen, Astellas, AstraZeneca, Baxter, Bayer, Biogen Idec, BMS, Celgene, Eisai, Eli Lilly, Gilead, GSK, J&J, Kyowa Hakko, Merck, Mitsubishi, Mylan, Novartis, Pfizer, Roche, Sanofi, Shire, Takeda, Teva, and Valeant, amongst many others.
The report also includes numerous tables and figures that illustrate the trends and activities in clinical stage partnering and deal making since 2016.
In addition, a comprehensive appendix of all clinical stage deals since 2016 is provided organized by partnering company A-Z, deal type, therapy focus and technology type. Each deal title links via Weblink to an online version of the deal record and where available, the contract document, providing easy access to each contract document on demand.
In conclusion, this report provides everything a prospective dealmaker needs to know about partnering in the research, development and commercialization of clinical stage products and compounds.
Global Clinical Stage Partnering Terms and Agreements in Pharma and Biotech 2016 - 2023 includes:
Trends in clinical stage dealmaking in the biopharma industry since 2016
Analysis of clinical stage deal structure
Access to headline, upfront, milestone and royalty data
Case studies of real-life clinical stage deals
Access to over 2,900 clinical stage deals
The leading clinical stage deals by value since 2016
Most active clinical stage dealmakers since 2016
The leading clinical stage partnering resources
In Global Clinical Stage Partnering Terms and Agreements in Pharma and Biotech 2016 - 2023, the available contracts are listed by:
Stage of development at signing
Specific therapy target
Analyzing actual contract agreements allows assessment of the following:
What are the precise rights granted or optioned?
What is actually granted by the agreement to the partner company?
What exclusivity is granted?
What is the payment structure for the deal?
How are sales and payments audited?
What is the deal term?
How are the key terms of the agreement defined?
How are IPRs handled and owned?
Who is responsible for commercialization?
Who is responsible for development, supply, and manufacture?
How is confidentiality and publication managed?
How are disputes to be resolved?
Under what conditions can the deal be terminated?
What happens when there is a change of ownership?
What sublicensing and subcontracting provisions have been agreed?
Which boilerplate clauses does the company insist upon?
Which boilerplate clauses appear to differ from partner to partner or deal type to deal type?
Which jurisdiction does the company insist upon for agreement law?
Key Topics Covered:
Chapter 1 - Introduction
Chapter 2 - Why do companies partner clinical stage compounds?
2.2. The role of clinical stage partnering
2.2.1. In-licensing at clinical stage
2.2.2. Out-licensing at clinical stage
2.3. Difference between phase I, II and III stage deals
2.4. Reasons for entering into clinical stage partnering deals
2.4.1. Licensors reasons for entering clinical stage deals
2.4.2. Licensees reasons for entering clinical stage deals
2.5. The future of clinical stage partnering deals
Clinical stage deal strategies and structure
3.2. At what stage do companies partner?
3.2.1. Partnering early in pharmaceutical/biotech
184.108.40.206. Discovery and preclinical stage partnering case studies
3.2.2. Partnering later in pharmaceutical/biotech
220.127.116.11. Clinical stage partnering case studies
3.3. Early and later stage partnering - a risk/cost comparison
3.4. What do companies spend on clinical stage partnering?
3.5. Pure versus multi-component partnering deals
3.6. Pure licensing agreement structure
3.6.1. Example pure licensing agreements
3.7. Multicomponent clinical stage partnering agreements
3.7.1. Example multicomponent clinical stage clauses
Chapter 4 - Clinical stage partnering payment strategies
4.2. Clinical stage payment strategies
4.3. Payment options
4.3.1. Headline values
4.3.2. Upfront payments
18.104.22.168. Conditionality of upfront payments
4.3.4. Convertible loans
4.3.6. R&D funding
4.3.7. Licensing fees
4.3.8. Milestone payments
4.3.9. Royalty payments
22.214.171.124. Issues affecting royalty rates
126.96.36.199. Royalties on combination products
188.8.131.52.a. Case study 12
184.108.40.206. Guaranteed minimum/maximum annual payments
220.127.116.11. Royalty stacking
18.104.22.168. Royalties and supply/purchase contracts
4.3.11. Option payments
Chapter 5 - Trends in clinical stage deal making
5.2. Clinical stage partnering over the years
5.2.1. Trends in phase I deals since 2016
22.214.171.124. Attributes of phase I deals
5.2.2. Trends in phase II deals since 2016
126.96.36.199. Attributes of phase II deals
5.2.3. Trends in phase III deals since 2016
188.8.131.52. Attributes of phase III deals
5.3. Clinical stage partnering by deal type
5.4. Clinical stage partnering by disease type
5.5. Partnering by clinical stage technology type
5.6. Clinical stage partnering by most active company since 2016
Chapter 6 - Payment terms for clinical stage partnering
6.2. Guidelines for clinical stage payment terms
6.2.1. Upfront payments
6.2.2. Milestone payments
6.2.3. Royalty payments
6.3. Clinical stage payment terms - deal data analysis
6.3.1. Public data
6.3.2. Survey data
6.4. Payment terms analysis
6.4.1. Clinical stage partnering headline values
6.4.2. Clinical stage deal upfront payments
6.4.3. Clinical stage deal milestone payments
6.4.4. Clinical stage royalty rates
Chapter 7 - Leading clinical stage deals
7.2. Top clinical stage deals by value
Chapter 8 - Top 25 most active clinical stage dealmakers
8.2. Top 25 most active clinical stage dealmakers
Chapter 9 - Clinical stage partnering contracts directory
9.2. Clinical stage deals with contracts since 2016
Chapter 10 - Clinical stage deal making by development stage
10.2. Deals by clinical stage
Appendix 1 - Clinical stage dealmaking by companies A-Z
Appendix 2 - Clinical stage dealmaking by industry sector
Appendix 3 - Clinical stage dealmaking by stage of development
Appendix 4 - Clinical stage dealmaking by therapy area
Appendix 5 - Clinical stage dealmaking by technology type
For more information about this report visit
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