In the rapidly evolving biopharmaceutical market, the journey from laboratory discovery to clinical manufacturing presents a formidable array of challenges. As the industry further embraces antibody-based therapeutics, the imperatives of cost-efficiency and speed-to-clinic are now more than ever riddled with hurdles in the form of accessibility, cost management, scale-up, regulatory compliance, and the rigorous demands of quality control and assurance. Many of these novel therapeutics are making their way into the clinic by way of small or emerging biotech innovators with limited internal resources, who are often developing a therapeutic as first-time entrepreneurs or as part of a team who are new to the special challenges of startups.
Before initiating human trials for a pharmaceutical product, there is a crucial need to invest in chemistry, manufacturing, and controls (CMC) development to ensure the clinical product meets established quality manufacturing criteria. The main goal of CMC is to ensure the quality of the pharmaceutical product throughout its development stages. Regulatory bodies demand comprehensive standards to verify consistency in identity, safety, quality, stability, and potency of the product used in clinical trials and future comparison to the batches manufactured for market distribution to maintain ongoing assurance. This vital information forms the basis for several regulatory filings — including the Food and Drug Administration's investigational new drug (IND) application and biologics license applications (BLA) in the United States and the EU’s investigational medicinal product dossier (IMPD) and applications for marketing authorization.1 Without the deep resources of large pharmaceutical companies, relatively small oversights in this area can lead to drastic consequences for smaller firms.
The complexity of meeting these regulatory criteria multiplies when utilizing multiple outsourcing partners for the discovery and CMC development phases of a program. This can be further compounded for small or emerging biotech innovators as they attempt to manage costs and ensure they are making the absolute best use of funding capital, all while attempting to maintain crucial development and production timelines. However, these challenges can be significantly mitigated by engaging a single partner equipped to pilot the discovery-to-clinic journey.
Incentives for Outsourcing Biologics R&D
One of the major challenges facing emerging biotechs during drug discovery is establishing the optimal balance between speed and cost. R&D, essential to fueling a biotech’s pipeline, is both expensive and exceptionally high risk — even should a putative candidate eventually prove successful, it will take years to show a return on this early research investment. Yet its criticality to the overall pipeline means that the budget for this work can only be stretched so far. This is further complicated by the variable nature of research work — timelines, budget, and staffing requirements can be difficult to predict, requiring dynamic resourcing, which is rarely straightforward within budgets where costs and headcount are fixed.
In such cases, outsourcing aspects of drug discovery becomes advantageous, allowing a more flexible use of budget and often bringing down overall R&D costs without slowing the pace or reducing the output of drug discovery. It can also allow emerging biotechs to access specialized skill sets and state-of-the-art technologies that would be prohibitively expensive to develop in-house.
As drug discovery becomes more specialized, it is often preferable to rely on outsourcing partners who are familiar with the special challenges of discovery. For example, for companies developing novel antibodies, Alloy Therapeutics offers a royalty-free, humanized transgenic mouse discovery platform, which has been carefully engineered to produce maximum diversity of unique human antibodies that bind to the target of interest, with broad epitope coverage and high affinity. From here, Alloy Therapeutics can further leverage advanced AI / ML technologies to screen for the best hits before conducting further antibody engineering and a full range of in vitro and in vivo testing to develop viable therapeutic candidates.
Challenges in the Translation from Discovery to CMC
Upon identifying viable lead candidates late in the discovery process, emerging biotechs face a new set of challenges related to the transition from discovery into CMC development and clinical trials. This translational gap requires strategic long-term planning and decision-making, especially as funds begin to dwindle. At this stage, innovators must begin developing their program’s CMC. This begins with an assessment of their molecule’s manufacturability and subsequent CMC development stages which are often critical data requirements to support further fundraising and encompass further costly and sometimes time-consuming milestones. These steps, including protein expression, cell line development, and process, analytical, and formulation development, are critical stepping stones to preclinical and clinical material supply and central to the core principles of a robust CMC strategy — demonstrating the ability to reliably manufacture a consistently reproducible therapeutic antibody at scale.1 While innovators are experts in their field, they are often less familiar with CMC development and manufacturing. Because they are often navigating this aspect of the industry for the first time, they rely on their CMC partners and consultants to make good scientific decisions on their behalf.
Scalability is crucial and requires early planning to ensure that the transition from laboratory-scale processes to clinical-scale production is feasible and efficient. Getting this right can significantly reduce the risk of later redesigns or process changes that might delay clinical trials at a significant cost. It also allows for more accurate forecasting of production costs of goods and timelines, paramount to attracting further investment and setting realistic expectations with existing stakeholders. The importance of incorporating scalability into early development stages to align with regulatory expectations is not to be understated. This foresight can streamline regulatory approvals and facilitate smoother transitions to later development stages. At this point, the support of an outsourcing partner adept at navigating the regulatory landscape can provide the competitive edge that makes the difference between a program’s failure or success.
Maintaining momentum is crucial for programs at this juncture, as failure can lead to significant losses in time and resources. Often lacking the necessary capital, manpower, or in-house expertise, most emerging biotechs find performing CMC in-house unfeasible, necessitating the selection of another outsourcing partner.
This selection is critical, as signing a contract with a contract development and manufacturing organization (CDMO) represents a notable risk for an emerging biotech, representing an enormous upfront financial commitment, often with fee-for-service terms that allow for costly budget creep over time. At this stage, the innovator should also consider the risks of being “locked in” to working with the same CDMO throughout development and CGMP manufacturing via CDMO process ownership, which can incur exorbitant penalties to tech transfer out to a new manufacturing partner.
Instead, emerging biotechs may prefer to consider a CDMO partner like Wheeler Bio, who take a vastly different, cost-efficient, and innovator-centric approach that reduces risk to the emerging biotech.
Wheeler Bio steps in during Alloy Therapeutics’ later-stage development work; integrating the translational steps between discovery and CMC development and manufacturing using a well-characterized CMC platform to enhance the capital efficiency of pre- and post-IND pipeline management. This unique integration of discovery and CMC allows biotechs to get a head start on their journey to the clinic and maintain developmental momentum. Through its Portable CMC® platform for antibody products, Wheeler Bio helps biopharma companies engage high-quality, purpose-built resources to create a seamless transition from early-stage development to manufacturing faster, more flexibly, and more cost-effectively than traditional CDMO models.
The true power of Portable CMC® is two-pronged: its modularity and its use of stable bulk cultures (SBCs) for early development, lead selection, Toxicology material supply, and even CGMP manufacturing. Portable CMC® is designed to accommodate antibody and antibody-like programs with ease, allowing innovators to choose the modular service packages that best fit their CMC development priorities, complementing any in-house capabilities, and aligning with their development milestones to maximize efficient use of funding, while keeping programs on track. Moreover, Wheeler Bio’s use of SBCs for the generation of reliable, reproducible, and representative clinical trial materials in lieu of traditional clonal cell line development eliminates some of the cost-associated risks that can so often derail programs in their infancy.2
Alloy Therapeutics & Wheeler Bio's PHASE™ Partnership
Juggling multiple outsourcing partners can lengthen timelines, increase project dependencies, and complicate regulatory documentation, posing further challenges to emerging biotechs. While selecting a single "end-to-end" partner might therefore seem appealing, this too often comes with its own compromises, including a lack of specialized expertise or access to next-generation technology platforms.
Enter the PHASE™ platform, a single-source discovery-to-clinical-manufacturing solution borne from the integrated partnership of Alloy Therapeutics and Wheeler Bio. Together, Alloy and Wheeler are paving the way for a streamlined, cost-effective, and efficient pathway from discovery to CGMP clinical material production. PHASE™ effectively positions two partners as one: unlike traditional CDMO models, Wheeler can begin CMC development during Alloy’s later-phase R&D work. This bridges discovery to CMC with unprecedented efficiency, creating a unique opportunity for innovators to maintain their program’s momentum as they transition from the discovery phase into preclinical and eventual clinical manufacturing.
The PHASE™ partnership is a holistic service model that enables innovators to capitalize on Alloy Therapeutics’ foundational biologics discovery technologies in direct conjunction with Wheeler Bio’s preclinical development and clinical manufacturing expertise. This strategic collaboration ensures a more streamlined, economical, and timely advancement through the critical phases of candidate selection to the production of pre-clinical Toxicology material and CGMP-compliant clinical drug substance and drug product. By integrating Alloy Therapeutics’ specialized expertise in antibody discovery with Wheeler Bio’s Portable CMC® platform, the partnership provides valuable discovery, development, manufacturing, and regulatory support within a single unified offering.
The PHASE™ program simplifies the complex journey from discovery to clinic and aims to significantly reduce the cost, time, and risk associated with the development and manufacture of therapeutic antibodies without compromising quality, efficacy, or safety. Alloy and Wheeler Bio do this by starting CMC development much earlier in the discovery process, for example, Wheeler leverages the Portable CMC® process platform to provide CHO pool-derived antibody candidate material for the Alloy in vivo discovery studies. This approach significantly mitigates the risks of working with multiple outsourcing partners by ensuring a seamless technology transfer from discovery into preclinical development. Through this collaboration, innovators are afforded a stabler and more efficient pathway for bringing their discoveries to human trials, thereby accelerating the overall drug development cycle and enhancing the potential for successful therapeutic outcomes.
Synergy is the Key to Better Biotherapeutic Development
Alloy Therapeutics and Wheeler Bio’s PHASE™ program offers several benefits to partners, including dollar-for-dollar reductions in Alloy Therapeutics’ commercial milestones matching Wheeler Bio's Portable CMC® service fees, complimentary CMC consulting services, CHO pool generation at no cost, significant savings on initial payments, and manufacturing slot reservations for Alloy partners. By combining and overlapping Alloy Therapeutics’ discovery capabilities with Wheeler Bio's development and manufacturing services, the partnership promises to significantly expedite the path of new therapies to clinical trials, thereby accelerating the delivery of lifesaving drugs to patients. This approach reflects a broader industry trend toward integrated solutions that can address the multifaceted challenges of biopharmaceutical development, from discovery through to first-in-human trials.4
PHASE™ is a reimagining of the traditional pathway from discovery to the clinic. Through this partnership, emerging biotechs can expect faster turnaround times and more candidates moving into trials. The unique benefits for Alloy-Wheeler PHASE™ partners — ranging from accessibility to unique technology platforms and favorable pricing to complimentary CMC consulting — are tailored to create a more accessible development process for innovators while simultaneously fostering more rapid patient outcomes, setting a new standard for success in biotherapeutic development. Conscious of the monetary challenges associated with developing biologics, PHASE™ allows innovators to stage their workflows to match currently available funding, ultimately creating value in the form of proof of concept to support subsequent stages of fundraising. PHASE™ not only accelerates the journey from discovery to clinic and embodies the collaborative spirit necessary to drive innovation in modern biotech.
References
- “Chemistry, Manufacturing, and Controls (CMC) Advice and Management.” Propharma. Accessed 29 Feb. 2024
- “Opportunities to Enhance the Capabilities of the Biotechnology Regulatory System.” In Preparing for Future Products of Biotechnology. National Academies Press. Washington DC. 28 Jun 2017.
- Li, Zhijie et al. “Simple piggyBac transposon-based mammalian cell expression system for inducible protein production.” Proc. Natl. Acad. Sci. USA. 110: 5005–5009 (2013).
- Rantanen, Jukka and Johannes Khinast. “The Future of Pharmaceutical Manufacturing Sciences.” J. Pharm. Sci. 104: 3612–3638 (2015).
