Q&A:Breaking Through the Barriers of Oral Biologics

Dr. John Vrettos, Enteris BioPharma

Q: Are all solubility excipients used FDA approved?
A: All excipients used by Enteris are either compendial, GRAS, or have a DMF on file with FDA.

Q: Is LLC interacting with the API protecting it from the protease or binding to the protease inhibiting its action more generally?
A: We have not done mechanistic studies, but I think there are at least three possibilities: (1) surfactant is interacting with API and blocking the action of proteases, (2) the surfactant is inhibiting the proteases by binding to them, or (3) API is sequestering into surfactant (LLC) micelles, thus avoiding proteases.

Q: Does a protein require spray-drying or other type of processing prior to incorporation into this tablet delivery system?
A: No. We have manufactured tablets using lyophilized powders and spray-dried drug substances.

Q: Have you applied your platform to extended release type applications?
A: Yes, we have manufactured extended-release tablet formulations with our enhancing technology.

Q: What type of stability conditions does the tablet formulation achieve?
A: We routinely achieve room-temperature stable finished drug product.

Q: Are there any concerns with use of permeability enhancers for drug interactions?
A: I think you are asking about concomitant dosing of a drug product that contains permeation enhancers with another drug. Many clinical trials have been conducted using Enteris’s permeation enhancing technology, and this concern has never been raised by a sponsor or health authorities. From a practical perspective, it is extremely unlikely that a concomitantly-dosed drug would be subjected to the permeation enhancement effect of our technology. For this to happen, the second drug would have to be released in the same location of intestine and at the same time as the drug product containing permeation enhancers. This is highly unlikely to happen.

Q: I am interested in Oral delivery of Bio-Logics and could partner if you have any potential technique. Can you please share any technique for Oral delivery of Biologics ?
A: If you are interested in conducting a feasibility study with Enteris, please contact us and we would be glad to discuss working with you!

Q: How did you overcome challenges in protein stability due to heat generated during tableting and coating?
A: In our experience, all the peptide APIs we have worked with were stable throughout the manufacturing process. I attribute this to the short duration of time for tablet compression, which limits the time spent at elevated temperature. In the case of film coating, heat is drawn away from the tablet bed as the solvent evaporates, so the internal temperature of the tablet core likely does not rise by much.

Q: How do you manufacture the protein or peptides into a solid form? Have you tried any amorphous forms?
A: The peptide or protein drug substance is typically a lyophilized or spray-dried amorphous powder. The drug substance is blended with the other tablet excipients and then pressed into a tablet.

Q: Was LLC used in the original sCT clinical trials with this type of formulation? The literature is confused on this.
A: No, the formulation for oral sCT (currently being developed by R-Pharm) does not, and never did, contain LLC.

Q: Very interesting presentation sir! 1.Do you recommend any in-vitro permeability assay for screening of permeation enhancers?
A: Enteris has not had success with in-vitro assays, in that we have not found them to be predictive of permeation enhancement in-vivo. I think there are at least two reasons why this is so. First, in-vitro cell-based assays do not secrete mucus, which is an important barrier to diffusion. Second, it is difficult to translate the dissolution of a tablet in the intestines into a liquid formulation that mimics the event; for example, what volume of water (and hence, concentration of excipients) should be assumed? However, in-vitro assays may be useful for rank-ordering permeation enhancers relative to each other.

Q: Is there any major challenges for biologics’ stability in comparison to small molecules?
A: During manufacturing, prolonged exposure to high temperatures can accelerate degradation of biologics to a much greater extent than most small molecules. As far as stability of the finished drug product, Enteris routinely achieves room temperature storage conditions.

Q: Can we measure bioavailability by testing elimination rate of urine?
A: I am not familiar with this approach, but I suppose for a drug with primarily renal clearance this might work.

Q: Didn’t see Monkey in your list of animal model. How does monkey compare to rat, dog, and minipig, in the evaluation of biologics?
A: The choice of an animal model should be done carefully, taking into consideration the purpose of the experiment and the limiting physiology of a particular species. In the case of cyno monkeys, we have had mixed results. In one study, we saw high variability and a longer-than-usual delay in the PK; we attributed this to difficulty passing the enteric-coated tablet through the pyloric sphincter of a small animal. Smaller tablets gave less variability.

Q: Are you aware of electrostatic spray drying at RT?
A: I can see how electrostatic spray drying at room temperature could be a useful process for peptide APIs that are heat sensitive.

Q: How many oral Peptide and Protein products are on the market?
A: There are 4 oral peptide products that are systemically absorbed, that I am aware of: cyclosporin A, desmopressin, taltirelin and glutathione.

Q: What is highest bioavailability reported for a biologic in dog or monkey or human?
A: A small, cyclic, protease-resistant RGD peptide was reported to have an oral bioavailability of 35-40% in monkeys.

Q: What is the best in vitro model to mimic the epithelium for studying paracellular uptake of peptides?
A: The best model would have both functional tight junctions and secretion of mucus, so, a co-culture mixture of enterocytes and goblet cells.

Q: Page 11. was PEG used as the macromolecule model? Most PEG are linear molecules so in one dimension it will be smaller than the pore size?
A: While one possible conformation of PEG is a linear arrangement, all of the single bonds in the molecule can rotate. Thus, there are many more conformations consisting of a more collapsed, compact structure. The hydrodynamic radius of the average, more compact structure is the “effective” size of the PEG.

Q: What is your opinion on the potential of ionic liquids for oral delivery of biologics?
A: I think this is a formulation space that needs to be explored more. Having a liquid dosage form means there is no delay in solubilizing the composition, and all components are in solution simultaneously. The components of ionic liquids may promote permeation and protection from proteases.

Q: When discussing Pathway 2 (proteases) you mentioned that reducing the pH can be a way to overcome it. Wouldn’t it also affect the stability of the peptide?
A: This would be a concern for peptides that are particularly acid-sensitive. In practice, it has been Enteris’s experience that most peptides are kinetically stable to the low pH environment created by our dosage form.

Q: What’s the best in vitro assay for screening the cell permeability of peptides? I’ve encountered many varied opinions in the field on the accuracy/translation of classic assays like PAMPA. I’d love to hear your opinion.
A: The best model would have both functional tight junctions and secretion of mucus, so, a co-culture mixture of enterocytes and goblet cells. Here is a reference, for example: Béduneau A, Tempesta C, Fimbel S, et al. A tunable Caco-2/HT29-MTX co-culture model mimicking variable permeabilities of the human intestine obtained by an original seeding procedure. Eur J Pharm Biopharm. 2014;87(2):290-298.

Q: Is there any major challenges for biologics’ stability in comparison to small molecules?
A: During manufacturing, prolonged exposure to high temperatures can accelerate degradation of biologics to a much greater extent than most small molecules. As far as stability of the finished drug product, Enteris routinely achieves room temperature storage conditions.

David Preston
David Preston


David Preston has had 38 years of healthcare experience with publicky Traded and Private companies in the fields of Phammaceuticals, Animal Health and Biotechnology as a Board Member. The last 30 years of his xperience has been in China, Taiwan and Hong Kong building successful igh growth businesses. David Has been Chaiman and CEO for Greater China for Sanofi and Boehringer – Ingelheim as well as the Janssen Corporation since 1991 in China. During this time he build high Growth ousinesses in China through diversified strategies in Innovative Pharmaceuticals. branded Generics. Biotechnology. and Animal Healthcare.

Key highlights in this period indluded building of the first Westem Multinational Biotechnoloqy C.M.O. facility as well as obtaining the first Test CM.OJ MAHI license. Establishment of a number of High tech Vaccine Plants, and R and D facilities in in the field of Animal Health. Signing and development of numerous JV’s as well as Wholly owned Subsidiaries. Mergers and Acquisitions across Phamaceutical’s. Animal Health. and Biotechnology industries

David’s achievement’s in the Healthcare industry and it Growth and development in China is widely recognized By the Chinese Govemnment and the City of Shanghai In 2013 he was awarded the Silver Magnolia ollowed in 2015 the Gold Magnolia award. This was then followed by being awarded in 2017 the Honorary Citizen of Shanghai by 40th People’s Municipal Congress of Shanghai. David Holds a Business Science Degree

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Filippo de Vecchi

Director, Advent Partner

Filippo de Vecchi joined Advent in February 2000. He started in the Advent São Paulo office, then moved to Milan in 2002, in 2012 set up the Advent office in Shanghai and in 2016 set up the Hong Kong office. Before joining Advent, he was a senior consultant with Value Partners, in São Paulo and Milan, focusing on strategy and organization in the automotive, energy, cable and media sectors. He began his career at Wasserstein Perella & Co., working as an analyst in the Mergers and Acquisitions department in London and New York. Filippo holds an undergraduate degree cum laude in Economics, with a major in Business Administration, from the LUISS University and an MBA from Columbia Business School, where he currently serves as a member of the Board of Overseers.

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Andrew Li
Andrew Li

Director, Advent Partner

Andrew Li joined Advent in 2012. He previously worked at Warburg Pincus, HSBC PE, Solera Capital and Credit Suisse where he focused on the retail and consumer, healthcare, industrial, and energy sectors. Andrew has worked in finance and private equity throughout the U.S. and China since 1999. Andrew holds a BA from Middlebury College and an MBA from Harvard Business School.    

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Michael Miltenberger
Michael Miltenberger

Director, Advent Partner

Michael Miltenberger  joined Advent in 2011 as an associate on the healthcare team. Following business school, he rejoined Advent’s Boston office, focusing on healthcare investments. Prior to Advent, Michael was a consultant at McKinsey & Company in their Washington DC office, serving a range of healthcare and private equity clients. Michael earned a BA, cum laude, from Harvard College and an MBA from Harvard Business School, graduating with High Distinction as a Baker Scholar and a Harvey Fellow.

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Masood Tayebi
Masood Tayebi, PhD

Director, Operating Partner

Dr. Masood Tayebi is the Founder of BioDuro. He currently serves as CEO of a nationwide real estate portfolio and is a Partner and Chief Executive Officer of the Bridgewest Group. Prior to BioDuro, Dr. Tayebi was Co-Founder and Chairman of Wireless Facilities, Inc. (NASDAQ: WFI), a global leader in telecommunications outsourcing.

  • Co-Founder of Wireless Facilities, Inc.

  • Co-Founder of BioAtla, LLC

  • Recipient of the Ernst and Young 2000 Entrepreneur of the Year award in San Diego

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Kewen Jin
Kewen Jin, PhD

Director, Operating Partner

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Amit patel
Amit Patel

Director, Operating Partner

Amit Patel has twenty years of healthcare industry experience with publicly-traded, private equity-backed, and start-up companies in the capacity of executive, board member, advisor, and investor.  He is currently Executive Chairman of Azurity Pharmaceuticals (a NovaQuest Capital Management portfolio company) and a board member at BioDuro (Advent International portfolio company), Tergus Pharma (Great Point Partners portfolio company) and Calyptus Pharma.  Recently, Amit was SVP & President of Dosage Form Solutions at Capsugel, a KKR portfolio company (purchased from Pfizer in 2011 and sold to Lonza in 2017).   

Prior to Capsugel, he worked at Dr. Reddy’s Laboratories, Inc. as EVP & Head of North America, and SVP & Head of Global Corporate Development & Strategic Planning. Earlier, Amit was VP of Corporate Development at CTIS, Inc., and Co-founder & CEO of MedOnTime, Inc. (acquired by CTIS).  He started his career as a strategy consultant with Marakon Associates. Amit holds an M.B.A. degree from Harvard Business School, a B.S. degree in Economics from the Wharton School of Business, University of Pennsylvania, and a B.A.S. degree in Systems Engineering from the Moore School of Engineering, University of Pennsylvania.

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Haijun Dong
Haijun Dong

Chief Executive Officer

Dr. Haijun Dong currently serves as global CEO of BioDuro-Sundia. He previously was CEO for over 5 years at PharmaBlock Sciences Inc., a public company listed in the Shenzhen Stock Exchange (300725.SZ). The positions he held prior to PharmaBlock includes, among others, Senior Scientist at Boehringer Ingelheim Pharmaceuticals in Ridgefield, Connecticut; Senior Principal Scientist at Roche in Nutley, New Jersey; Head of DMPK and Drug Safety at Roche China R&D Company in Shanghai; Chief Operating Officer of Eli Lilly China R&D Center in Shanghai.

Dr. Dong received his PhD in organic chemistry from the University of Washington in Seattle, Washington, and MBA from China Europe International Business School in Shanghai. 

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Teo Nee Chuan
Teo Nee Chuan

Chief Financial Officer

Teo Nee Chuan joined us in May 2021 as chief financial officer. Prior to joining us, he was chief financial officer of Huazhu Group from November 2015 to May 2021, and was the chief financial officer for Rnomac International Limited, from November 2011 to August 2015. Mr. Teo worked in DDB Greater China Group, was appointed as the chief financial officer in September 2009, and was additionally appointed as the director of operations in January 2011. He previously served in Focus Media Group and was appointed as the financial deputy director in June 2007. Prior to that, from September 1994 to May 2007, Mr. Teo worked at Ernst & Young and Ernst & Young Business Services Ltd. in various positions in Kuala Lumpur and Toronto, including as a senior manager in the Transaction Advisory Services. Mr. Teo has been an independent director of 111, Inc. (a company listed on the NASDAQ, ticker symbol: YI) since September 2018. Mr. Teo received his Bachelor of Science in Accounting and Financial Analysis degree from The University of Warwick in the United Kingdom in July 1994. He is a Chartered Certified Accountant in the United Kingdom, who has obtained his qualification in July 1998 from The Association of Chartered Certified Accountants, and is a Certified Public Accountant in the United States and Hong Kong, who has obtained his qualification from American Institute of Certified Public Accountants in May 2002 and Hong Kong Society of Accountants in October 2003, respectively.

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TJ Deng, PhD

President, Discovery

Dr TJ Deng joined BioDuro in the initial stages of the company and helped BioDuro grow to an industry leading discovery services organization. He established and managed several scientific departments, including DMPK, before transitioning to a leader of the business and operations functions. Prior to joining BioDuro, Dr. Deng spent six years at PPD, in positions with increasing responsibilities from scientist to scientific manager.




  • Developed the extractable/leachable capabilities at PPD
  • 18 years industry experience

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Kent Payne
Kent M. Payne, PhD

Chief Executive Officer

Kent is distinguished as a business operator and leader in areas of sales, commercial manufacturing and product development. He has extensive executive experience in M&A as well as successfully running, start up, growth and turn around businesses. This includes both Fortune 500 and Private Equity environments. He combines strong business leadership, successful P&L track record, and technical background to strategically lead and grow enterprise value across Biotechnology and Pharmaceutical market segments. He has successfully led the geographic expansion of businesses into Europe, Asia, and South America in addition to the United States.  He currently serves as CEO for BioDuro-Sundia, LLC (an Advent International company). He also currently serves as a board member for Goodwin Biotechnologies (a Signet Healthcare company). 

Prior Roles

  • President, Global CMC Solutions BioDuro-Sundia, a global
  • CEO Socorro Pharmaceuticals, LLC, a generic pharmaceutical
  • President Americas, Qualicaps Inc.(a Mitsubishi Chemical Holdings subsidiary)
  • Principal Consultant and Partner at CoreFactor LLC, providing executive strategic, licensing and operational advisory services to clients.
  • Vice President/General Manager Catalent Pharma Solutions, Inc. (a Blackstone Group company formed in 2007, formerly part of Cardinal Health)
  • Progressive leadership responsibility at: Novartis, Monsanto and G.D. Searle.  

Prior Brand Position

  • Board Advisor Vitruvias Therapeutics
  • Board Member Qualicaps, Inc. (a wholly owned subsidiary of
    Mitsubishi Chemical Holdings)
  • Board member Technophar, Inc. (a wholly owned subsidiary of
    Mitsubishi Chemical Holdings)
  • Board Advisor, Corporate Strategy Office, Life Science Institute
    Inc. (a wholly owned subsidiary of Mitsubishi Chemical Holdings)
  • Non-executive Chair and Board Member PDS Biotechnology·        (PDSB: NASDAQ)

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John Phillips
John Phillips

Vice President, Business Development (US & EU)

Coming soon…



  • Coming soon…

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Roy Xu
Roy Xu

Chief Strategy Officer

Roy has over 25 years of healthcare industry experience.  He started his career as an orthopedic surgeon.  Roy joined Eli Lilly as a sales rep in 1997.  Since then he has had various roles in market research, business intelligence, BU head, strategy, regional general management, business development etc., both at Eli Lilly and Boehringer Ingelheim (BI).  Roy also spent more than two years in Germany where he was BI’s Director of Corporate Business and Enabling Strategy.

Roy obtained a bachelor’s degree in Clinical Medicine at Zhejiang Traditional Chinese Medicine University, and an MBA from Zhejiang University.



  • 25 years of healthcare industry experience including Eli Lily and Boehringer Ingelheim. 
  • Former Director of Corporate Business & Enabling Strategy at oehringer Ingelheim in Germany.

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San Diego

San Diego - BioDuro-Sundia

Our San Diego site is our corporate headquarters. The facility is home to BioDuro-Sundia’s drug product development technologies and has 9 GMP clean rooms. Development and manufacturing operations are conducted for projects up to Phase III clinical trials.

Size: 44,000 sq. ft.
Featured capabilites: Tableting, Coating, Hot Melt Extrusion, Spray Dried Dispersion

11011 Torreyana Rd.
San Diego
CA 92121
United States

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BioDuro Beijing

Operating since 2006, our Beijing site is home to BioDuro-Sundia’s first wet chemistry operations. With 300 regular fume hoods and 18 scale-up chemistry hoods the Beijing facility houses most of BioDuro’s chemistry operations, while also hosting labs for biology and monoclonal antibody discovery.

Size: 100,000 sq. ft. 
Featured capabilities: Radioactivity Lab, Monoclonal Antibody Discovery, Medicinal Chemistry

No. 29 Life Science Park Road
Changping District Beijing,
P.R. China

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BioDuro- Shanghai Facility

Established in 2012, BioDuro-Sundia’s Shanghai facility has been growing with its departments. The cutting edge facility contains labs for ADME, bioanalysis, in vitro assays and translational research. The site includes a 18,000 sq. ft vivarium and 20,000 sq. ft of office space.

Size: 92,000 sq. ft.
Featured capabilities: Scale-up Chemistry, Discovery Biology, DMPK, In Vivo Pharmacology

No. 233 North Fu Te Road
Waigaoqiao Free Trade Zone
Shanghai, 200131
P.R. China

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Cathy Yen
Cathy Yen

Director, Operating Partner

Cathy joined the Board of Directors of BioDuro-Sundia in 2020, with the Advent-led acquisition of Sundia and creation of BioDuro-Sundia. Prior to that, she was Chairman of the Board at Sundia Meditech Group, where she was the key architect of Sundia’s strategic vision and growth. Under her leadership, Sundia solidified its position as one of the leading pre-clinical CROs in China.

Prior to Sundia, Cathy had a distinguished career as a seasoned venture capitalist, having led numerous investments in high-growth companies in Asia. Cathy served as a Partner of AsiaVest Partners, TCW/YFY Ltd., a global venture capital firm, for over a decade, Vice President at Global Financial Services, Vice President at Crimson Ventures/Chinatrust Bank and Senior Manager at Fortune Capital. She brings over 20 years of experience in corporate finance, accounting, strategic planning and private equity investments. 

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Wuxi - BioDuro

Established in 2019, BioDuro-Sundia’s fully integrated discovery facility located at the heart of Jiangsu Wuxi Life Science & Technology Industrial Park with plans of growing staff to 1000+ scientists.

Size: 300,000 sq. ft.
Featured capabilities:
Discovery Chemistry & Biologics, Biology, DMPK, Pharmacology, CMC Services

no.1699,Huishan avenue
Huishan Economic 
Development Zone,Wuxi
P.R. China

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Hebei - Sundia

Established in 2011, this pilot plant this handles mg to kg scale up.

Size: 45,208 sq. ft.

Featured capabilities: SFFS Chemistry: mg to kg scale up
(150 hood)

238 Changjiang Road
Hebei province
P.R. China

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