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Asembia 2025 

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Nancy Pollini is director of strategic accounts for language services at AMPLEXOR Life Sciences.

The call to reduce market entry times for life-saving new drug therapies is becoming more urgent. What constitutes best practice in managing translations in today’s regulatory affairs environment? Nancy Pollini reports.

Managing Local Language Regulatory Submissions

AbbVie Pedro Valencia ADCs

PE: How is AbbVie using novel cancer biomarkers to develop potential first-in-class ADCs for the treatment of advanced solid tumors?

We're constantly looking for biomarkers that can help us to do two key things. The first is to tackle cancer cells. and spare normal cells. We’re looking for specific antigens that are over-expressing tumor cells, and you see limited expression in normal cells. We want to make sure that target that’s over-expressed is critical for the survival of the cancer cell. Once you block it, you can actually drive a cancer cell death. That’s what we're looking for. In that perspective, c-Met is one of those biomarkers that is over expressing multiple tumor types such as lung, colorectal, gastric, and other GA tumors. We as an industry have tried to tackle c-Met in the past but have been unsuccessful. It would actually be successful to tackle what we call met, which is a gene inside the cell.

There’s this thing called met amplification, where the cancer cell produces multiple copies of the gene, and around 30% of patients have it. We can actually tackle that with small molecules. But once the gene becomes a protein and gets over-expressed in the cell, that over-expression is something we haven’t been able to target. For example, we know that on lung cancer, c-Met over-expression is about 25% to 50% in colorectal cancer, and it could be anywhere from 30% to 70% depending how you measure it, so it’s quite prevalent.

With ADCs, we’re trying to tackle c-Met over-expression on the surface of cancer cells. That was novel, and we can do it through ADCs. 706 has a target called SEZ6, and it’s a target that is over expressed in neuroendocrine cells or neuroendocrine neoplasms. When you think about it, multiple tumor types kind of have a subset of cells that are neuroendocrine driven. Small cell lung cancer is one of the few that has everything driven by neuroendocrine cells. The beauty of SEZ6 is over-expressing those cells and limited expression in normal cells. So, we can tackle it with an ADC and drive the results that we're seeing today.

PE: ADCs have redefined the treatment of cancer in recent years. Can you please discuss the promise of this emerging class and what the future may hold?

At the end of the day, ADCs work like a trojan horse. You have a good antibody that cancer cells are happy to receive, but once you hook into the cancer cell receptor, you deliver the payload, which is pretty much chemotherapy. It’s actually a highly potent version of the regular chemotherapy cancer patients are given on a regular basis. So, from that perspective, our goal is to replace chemotherapy. Our grand goal with ADCs is to replace good old, decades old chemotherapy that is really toxic for some patients. That’s how we see the redefinition of cancer treatment in the future with ADCs. So, what do we see in the future? Well, if you think about it, chemotherapy is being given in combination with other agents. In the future, we see ADCs being given in combination with chemotherapy. There will be one with other agents such as immuno-oncology agents. So, if you combine the ADC and the PD1s, you can start seeing that synergy come together and kind of start really dreaming about cures for the patients. All in all, we're super excited about ADCs replacing chemotherapy. 

In an interview with Pharm Exec Associate Editor Don Tracy, Pedro Valencia, VP, Solid Tumor Pipeline Strategy & Execution, AbbVie, discusses using novel cancer biomarkers to develop potential first-in-class antibody drug conjugates (ADCs) and the promise that they offer. 

Utilizing Biomarkers to Develop First-in-Class Antibody Drug Conjugates to Treat Advanced Solid Tumors

No biopharma company wants to receive a complete response letter (CRL) on a drug that has taken years to test and major cash to develop—let alone a CRL an executive did not expect.

That’s what happened to Replimune Group, Inc., on July 22, when the FDA issued a CRL for the company’s advanced melanoma treatment, RP1. The move surprised the company, which said none of the issues raised in the CRL were addressed in mid- and late-cycle reviews.

The decision also surprised Wall Street analysts and investors. The news dropped before the market opened on July 22, and the company’s stock proceeded to plunge nearly 77%, from about $13-a-share to around $3-a-share. Prior to the news, the investors expected RP1 to be approved on accelerated approval pathway and described the rejection as a surprise.

A similar but perhaps less dramatic story played out earlier in July, when Capricor Therapeutics, Inc. received a CRL for its investigational Duchenne muscular dystrophy therapy, citing outstanding items in the chemistry, manufacturing, and controls part of the application, which the company claimed it had already addressed.

Both organizations have since requested Type A meetings with FDA officials to discuss their paths forward.

Replimune and Capricor are individual situations but, taken together, they raise new questions for both the biopharmaceutical industry and investors alike. Pharma and biotech obviously rely on FDA approval, and these recent announcements have many people wondering what to expect next. How will these changes impact investors and how pharma companies communicate with them? More importantly, how can industry and investors adjust their strategies for these new rules?

How can pharma companies prepare and strategize based on recent unexpected FDA decisions?

One factor is that leadership at the FDA has changed since Replimune submitted its BLA under the accelerated approval pathway in November 2024. Many senior regulators have left or been forced out as part of a leadership and staff shakeup. Meanwhile, the agency has also pushed transparency, recently publishing hundreds of CRLs from past years, although only those for drugs that were ultimately approved.

So now biopharma companies with drugs in the review process and an approaching PDUFA date are wondering: Will we be next?

"This decision at the end of the process is difficult,” said Replimune CEO Sushil Patel , Ph.D., in a July 23 interview with BiotechTV. “I do think it’s going to make it extremely difficult for small companies such as us—investors also—to have trust that they are going to put money into companies with innovative products, if they feel that things could change late in the process. ... There's also patients waiting at the end of the day."

It’s a challenging time for drug developers because of this uncertainty, especially those that based their development strategies and investments on the communications they had with FDA officials from the prior administration, said Craig Lipset, co-chair, Decentralized Trials & Research Alliance, in an email interview with 

“It raises questions for developers today as to whether past understandings still hold true, as well as the potential risks and benefits of re-engaging with FDA on active development programs based on those past agreements,” Lipset said.

The CRL to Replimune’s oncolytic immunotherapy candidate, RP1, did more than derail a priority review. It jolted investors and sparked questions about how the agency is communicating expectations. The timeline below tracks the pivotal regulatory and market moments that led to and followed the CRL.

For biopharma leaders, it’s a case study in why planning for multiple regulatory scenarios has never been more critical. Here’s a timeline of events:

: Replimune announces it has submitted its biologics license application (BLA) for RP1 under the accelerated approval pathway and that the FDA has granted Breakthrough Therapy designation for RP1 plus nivolumab in anti–PD-1–failed advanced melanoma.

: FDA accepts the BLA and grants Priority Review, setting a PDUFA action date of 

; FDA says no advisory committee is planned and no review issues are identified at that time.

 Replimune reiterates Priority Review status and the July 22 PDUFA date in its quarterly report.

 Vinay Prasad, MD, a hematologist oncologist, is named new lead for the FDA’s Center for Biologics Evaluation and Research.

: Investor optimism grows; Replimune shares rise about 32% in the weeks leading up to the decision.

: Replimune publicly discloses the CRL; press release states FDA found IGNYTE was “not an adequate and well-controlled” study and could not be “adequately interpreted” due to patient heterogeneity. Replimune CEO Sushil Patel, PhD, responded: “The issues highlighted in the CRL were not raised by the agency during the mid- and late-cycle reviews. Additionally, we had also aligned on the design of the confirmatory study.” The company stock plunged up to 77%, triggering multiple trading halts; shares ultimately fell below $3. Replimune requested a Type A meeting with FDA within 30 days to discuss the path forward.

Federal agency priorities always change when new presidential administrations take over, and in 2025, many high-profile regulators left or were forced out.

One of those high-profile officials who left was Peter Marks, MD, the former head of FDA’s Center for Biologics Evaluation and Research (CBER). His replacement is Vinay Prasad, MD.

When Prasad’s appointment was announced in early May, the biotech industry held its breath, because it indicated a tougher road ahead for cancer and rare disease developers. In past comments and writings, Prasad argued the FDA leaned too heavily on surrogate endpoints that don’t extend lives meaningfully and that drugs often cost too much for marginal benefit. His scholarship called for “more convincing clinical evidence.” His appointment immediately rattled markets, sending shares of cell and gene therapy companies sharply lower.

When the Replimune CRL was released, Wall Street observers believed that Prasad’s leadership of CBER was a factor in the surprise decision. According to a report published in 

analysts said Prasad likely played a “key role” in the decision.

Another factor in the changing world of FDA reviews to note is that in the event a biopharma company’ receives a CRL, it will probably go public.

Just prior to the Replimune announcement, the FDA revealed plans to publish CRLs as part of an initiative to embrace “radical transparency.” The agency published over 200 CRLs from 2020 to 2024, and FDA Commissioner Martin Makary, MD touted the initiative as a chance to provide clarity and predictability. for drug developers and capital markets.

“Today we’re one step closer to delivering it to them, with an ultimate goal of bringing cures and meaningful treatments to patients faster,” he said.

For now, questions remain on what impact the transparency initiative will have going forward, said Monica Gorman, currently the managing director at Crowell Global Advisors in Washington, DC, in an interview with 

 The CRLs that were published were older, and questions remain about what it means to publish them in real time, including for drugs that ultimately are not approved.

“There are very practical questions,” said Gorman, who is also former special assistant to the president for manufacturing and industrial policy and co-chair of the White House Supply Chain Disruptions Task Force. “Are there enough people to do the redactions? Obviously, the industry is going to have a lot of questions about confidential business information, trade secrets, and how all of that is going to be redacted. It’s difficult to know how the industry is going to respond from an investment standpoint until everyone has a better sense of what this actually means.”

Harpreet Singh, MD, former FDA division director of oncology and current chief medical officer at Precision for Medicine, called the move to make CRLs public a step toward greater transparency.

“It’s a testament to the agency’s evolving commitment to data sharing,” she said in an interview with 

. “Making these letters public can help demystify regulatory decision-making and offer sponsors and investors valuable insights. That said, the current approach focuses only on CRLs for drugs that were ultimately approved, leaving out many instructive examples tied to programs that didn’t advance. Having issued CRLs during my time at the agency, I’ve seen how these letters can bring value to sponsors by guiding development strategy, and broader disclosure could further their impact.”

While other have praised transparency as a positive, there’s another issue that needs to be considered: what impact the negative publicity of a CRL can have on a small biotech with a promising therapy clawing towards launch.

While CRLs are not a death sentence for a product and it’s entirely possible for a company to recover, timing is a major issue. Pharma companies and drug developers already have long timelines from development to launch. While many in the industry are calling for that timeline to be sped up, the FDA seems to be making moves to slow things down.

For companies that are getting good news, the slowdown is still frustrating. For a company receiving a CRL, it could be devastating.

But, as Gorman explains, transparency is an important reminder that regulators have to answer to more than just sponsors.

“There’s a history that goes back through a couple of administrations of a desire for FDA to have more transparency as to the reasoning behind CRLs,” Gorman said. “Obviously, a letter does not mean that a drug will not ultimately be approved, but it provides more information as to why it’s not being approved right now. There’s certainly an argument that FDA is representing both parties and it’s in the public interest to provide this information.”

The CRLs for Replimune and Capricor, leadership changes at key FDA centers and an unprecedented push for regulatory transparency are a signal that past assumptions may no longer hold; executives can’t bank on mid-cycle signals or legacy agreements anymore.

The path forward demands tighter evidence, documented alignment, and contingency plans that protect both timelines and investor confidence.

Reconfirm and document FDA alignment early.


Don’t rely on old understandings. Push for written clarity on endpoints, CMC expectations, and confirmatory plans—and keep meticulous records of every agreement.

Design trials and CMC packages to withstand scrutiny.


Minimize heterogeneity, tighten statistical plans, and stress-test “adequate and well-controlled” standards. Audit CMC sections with third parties to close gaps before FDA finds them.

Scenario-plan for a CRL—and assume it will be public.


Build parallel timelines (best/base/CRL), pre-draft Type A materials, and prepare redaction-ready documents. Coordinate legal, regulatory, and investor relations teams on same-day messaging.

Manage investors with a spectrum, not a binary.


Reset expectations away from “approve/deny.” Communicate multiple regulatory outcomes and capital implications, and brief key stakeholders on how you’ll respond if a CRL lands.

Dealing with uncertainty is nothing new for the pharmaceutical industry and its leadership. As Lipset, of the Decentralized Trials & Research Alliance, said, it’s up to the industry to push for clarity: “Sponsors must help communicate to FDA leaderships the urgency of regulatory clarity, as new leaders at the agency seem very committed to transparency and communications.”

Replimune Group, Inc. Replimune receives complete response letter from FDA for RP1 biologics license application. Replimune Investor Relations website. Published July 22, 2025. Accessed July 24, 2025. 

https://ir.replimune.com/news-releases/news-release-details/replimune-receives-complete-response-letter-fda-rp1-biologics

Capricor Therapeutics, Inc. Capricor Therapeutics provides regulatory update on Deramiocel BLA for Duchenne muscular dystrophy. GlobeNewswire. Published July 11, 2025. Accessed July 24, 2025. 

https://www.globenewswire.com/news-release/2025/07/11/3113911/0/en/Capricor-Therapeutics-Provides-Regulatory-Update-on-Deramiocel-BLA-for-Duchenne-Muscular-Dystrophy.html

Patel S. Interview: July 23, 2025. BioTechTV. Published July 23, 2025. Accessed July 24, 2025. 

https://www.biotechtv.com/post/sushil-patel-july-23-2025

BioPharma Dive. Vinay Prasad’s appointment at CBER signals tougher evidence standards for cancer and rare disease approvals. BioPharma Dive. Published May 8, 2025. Accessed July 24, 2025. 

https://www.biopharmadive.com/news/vinay-prasad-cber-fda-drug-approvals-research/747497/

Investor’s Business Daily. Replimune stock craters after surprise FDA rejection of melanoma treatment. Investor’s Business Daily. Published July 22, 2025. Accessed July 24, 2025. 

https://www.investors.com/news/technology/replimune-stock-surprise-fda-rejection-melanoma-treatment/

US Food and Drug Administration. FDA embraces ‘radical transparency,’ publishing complete response letters. FDA Press Announcements. Published July 10, 2025. Accessed July 24, 2025. 

https://www.fda.gov/news-events/press-announcements/fda-embraces-radical-transparency-publishing-complete-response-letters

A deep dive into the implications of the Replimune CRL that surprised insiders and investors, the role of new leadership at FDA’s CBER, and how industry can navigate the path forward.

Replimune CRL Fallout: How Biopharma Leaders Should Manage a New Layer of FDA Uncertainty

Emrelis and the Evolving Landscape of Antibody Drug Conjugates

, Neha Anand, Analyst, Biopharma Intelligence Services, Citeline, discussed how AbbVie’s newly approved antibody-drug conjugate (ADC), Emrelis, differentiates itself in a rapidly evolving oncology landscape. With rising competition in the ADC field—particularly in solid tumors—Anand highlighted Emrelis’ unique target, mechanism of action, and strategic positioning as key factors that set it apart. She also provided insight into what the approval signals about the FDA’s current regulatory posture, the potential impact on investor interest, and what a successful Phase III trial could mean for AbbVie’s long-term growth in precision oncology.

Pharmaceutical Executive: How does Emrelis stand out among other antibody-drug conjugates currently on the market or in development for solid tumors?

Emrelis stands out primarily due to its target and payload strategy, which positions it in a niche, biomarker-driven space. It’s specifically approved for MET-overexpressing non-small cell lung cancer, which differentiates it from other ADCs that tend to target broader indications.

Most other ADCs, like those directed at HER2 or TROP2, are focused on more common tumor types such as breast or gastric cancers. Emrelis, in contrast, addresses a distinct unmet need in the MET-overexpressing NSCLC patient population. Strategically, it is the first-in-class ADC targeting the MET protein in lung cancer, while many other ADCs are concentrated in different epithelial cancers.

Additionally, Emrelis offers a potential treatment option for patients who do not have MET gene mutations but do exhibit MET overexpression—further setting it apart in terms of patient population.

Another point of differentiation is the payload. Emrelis uses monomethyl auristatin E (MMAE), delivered via a cleavable linker. This enables a mechanism of action through microtubule disruption, unlike many of the newer ADCs that use DNA-damaging payloads, such as DXd-based topoisomerase inhibitors developed by companies like Daiichi Sankyo and AstraZeneca.

Taken together—its biomarker-driven targeting, first-in-class status, patient population specificity, and distinct mechanism of action—Emrelis represents a differentiated approach within the ADC landscape for solid tumors.

Emrelis stands out in the crowded antibody-drug conjugate (ADC) space by targeting a highly specific biomarker—C-MET overexpression in non-small cell lung cancer (NSCLC)—rather than pursuing broader tumor indications. Unlike ADCs such as those targeting HER2 or TROP2, which are used in breast or gastric cancers, Emrelis is designed for a niche patient subgroup with high C-MET protein levels but without MET gene mutations, a population with limited treatment options. This precision-targeting approach, combined with the use of the MMAE payload via a cleavable linker (which disrupts microtubules rather than causing DNA damage like some other ADCs), sets Emrelis apart both clinically and mechanistically.

The FDA’s accelerated approval of Emrelis signals a growing willingness to support biomarker-driven ADCs in solid tumors, particularly when addressing unmet needs. It reflects confidence in ADC safety and efficacy profiles and aligns with broader trends favoring precision medicine.

Emrelis is especially well-positioned to serve NSCLC patients representing roughly 25% of EGFR wild-type cases who overexpress C-MET but lack actionable mutations. While NSCLC remains the primary focus, success here could pave the way for expansion into other C-MET–driven solid tumors.

From an industry perspective, Emrelis’ approval is likely to fuel both investor enthusiasm and R&D momentum. For large pharmaceutical companies, it offers a blueprint to diversify oncology pipelines beyond traditional small molecules or immunotherapies. For biotechs, it validates the potential of novel ADC designs targeting underexplored antigens.

If Phase III trials meet their endpoints, Emrelis could become a new standard of care in C-MET high NSCLC and mark a strategic shift for AbbVie, establishing its credibility in solid tumor oncology and reinforcing its in-house ADC capabilities amidst rising competition from companies like Daiichi Sankyo and ImmunoGen.

Neha Anand, Analyst, Biopharma Intelligence Services, Citeline, discusses how Emrelis fits into the current antibody-drug conjugate landscape and what distinguishes its approach in biomarker-driven oncology.

Video Series

Embrelis Approval Highlights FDA Confidence in ADC Oncology Treatments

Pharmaceutical Executive: What does this approval signal about the FDA’s current posture toward emerging ADC therapies in oncology, especially for solid tumors?

The approval of Emrelis definitely signals that the FDA is very supportive of ADC therapies, particularly in oncology and for solid tumors with defined biomarkers. It also demonstrates the FDA’s willingness to grant accelerated approvals for ADCs targeting novel proteins, addressing clear unmet needs in specific patient subgroups. This aligns with the FDA’s broader trend of encouraging precision medicine approaches that match therapies to biomarker-driven populations. Additionally, this decision indicates that the FDA is now more confident about the safety and efficacy profiles of ADC platforms, paving the way for continued innovation in this field and potentially faster regulatory pathways for ADCs in the future.

 Emrelis stands out in the crowded antibody-drug conjugate (ADC) space by targeting a highly specific biomarker—C-MET overexpression in non-small cell lung cancer (NSCLC)—rather than pursuing broader tumor indications. Unlike ADCs such as those targeting HER2 or TROP2, which are used in breast or gastric cancers, Emrelis is designed for a niche patient subgroup with high C-MET protein levels but without MET gene mutations, a population with limited treatment options. This precision-targeting approach, combined with the use of the MMAE payload via a cleavable linker (which disrupts microtubules rather than causing DNA damage like some other ADCs), sets Emrelis apart both clinically and mechanistically.

Neha Anand, Analyst, Biopharma Intelligence Services, Citeline, explains how the approval of Emrelis marks a pivotal moment for ADC therapies in oncology, reflecting the FDA’s growing confidence in their safety and efficacy and accelerating the shift toward precision medicine in cancer treatment.

Emrelis Approval Highlights FDA Confidence in ADC Oncology Treatments

The rapid pace of innovation in oncology was displayed at the 2025 American Society of Clinical Oncology (ASCO) annual meeting, where research highlighted promising developments, including advances in immunotherapy and targeted therapies for rare cancers.

Scientific breakthroughs, including cell and gene therapies (CGT), personalized cancer vaccines, and targeted therapies, have helped to redefine approaches for certain cancers, contributing to the substantial progress achieved in 

The burgeoning oncology pipeline offers the potential to help accelerate that progress. More than 

 could launch over the next five years, and the number of oncology trial starts per year continues to climb—up nearly 

While the growing pipeline offers tremendous potential, the path from clinical development through to commercial launch and patient administration is complex and lined with challenges that can impact product success and access. To deliver on the promise of the therapies, developers must understand the market landscape and be prepared to overcome challenges, including those related to regulatory requirements, reimbursement, and patient access.

Navigating Diverse Regulatory Requirements

Drug development and regulatory considerations are closely intertwined, so it is imperative developers establish a robust strategy early in the clinical development process that involves engaging relevant regulatory bodies.

Proactive planning can help developers maintain compliance with global requirements, mitigate the risk of regulatory delays, and optimize the path to reach market more efficiently. For example, developers can leverage, when appropriate, mechanisms designed to facilitate a faster development process or make drugs available as quickly as possible, such as the FDA’s 

Priority Review, Breakthrough Therapy, Accelerated Approval, and Fast Track

 is 3.5 years faster when developers leverage one of the FDA’s expedited development or review pathways.

As part of their planning, developers should consider several key components: comparative analysis, Chemistry, Manufacturing and Controls (CMC) framework, and master protocols. The CMC framework, for example, requires comprehensive information about the manufacturing process, validation, data control and analytical methods, underscoring the importance of thorough documentation and adherence to guidelines and precedents.

Experienced partners can help developers navigate the regulatory landscape efficiently by facilitating productive interactions with regulatory bodies, assisting in preparing and submitting regulatory documents, ensuring compliance with regulatory frameworks, and supporting the design and execution of long-term follow-up studies.

Demonstrating Value: Supporting Efficient Launches and Access Globally

In the crowded oncology landscape, demonstrating a product’s clinical and economic value to key stakeholders, like payers, is critical. Developers should be to address fundamental payer questions, such as:

What am I currently paying for the treatment of this disease?

How is your drug better than the alternatives in my specific setting?

How much is the drug worth and why is it worth the cost?

Can I afford it and what part of my budget will I use to fund it?

What are the consequences of not funding?

Conducting a market landscape analysis and engaging payers early allows developers to gain feedback on target product profile, evidentiary needs, and value proposition, all of which can inform critical decisions, such as clinical trial design, endpoint selection, and data collection methodologies. The communication, coupled with clinical trial results, real-world evidence, and health economic research, will help developers create a robust evidence package that showcases the product’s value and addresses questions from key stakeholders related to clinical safety, efficacy, and cost-effectiveness.

As part of pre-commercial planning in the United States, developers should consider engaging in 

While the growing oncology pipeline offers tremendous potential, the path from clinical development through to commercial launch and patient administration is complex and lined with challenges that can impact product success and access. 

Nancy Pollini

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