By Arthur Tzianabos, CEO of Lifordi Immunotherapeutics, as part of the From The Trenches feature of LifeSciVC
Greetings from Lake Winnipesaukee in NH where I am at this time every year. It’s midsummer and vacation time for me and the family. In order to try and maintain a healthy work/life balance, I try and lead by example, but we know that this rarely goes according to plan in biotech. Once again, a Midsummer’s Madness is creeping in this year. Unlike March Madness, which is a fun weeks-long series of basketball games, Midsummer’s Madness marks that time of year on the Biotech calendar when you realize that September is just around the corner…not so fun. You know it will arrive with a roar as the mad dash toward year end begins. For some, a Midsummer’s Madness can be a Midsummer’s Nightmare.
At this point of the year, the JPMorgan conference seems like ancient history and you are looking into flights for JPM 2025. There you met with investors and analysts with the corporate milestones in hand and certainty on your mind. These goals were believable and achievable. Was that only six months ago? And was it only in June that you had your last Board meeting before the summer and shared the tremendous progress the company made in the first half of the year? This was followed by detailed plans for accomplishing the remaining goals over the next six months. Now that the September Board meeting is fast approaching, you ask yourself many important questions.
How is the company tracking toward the corporate goals? Should it be a red, green, or yellow circle beside each goal? Admittedly, these colors, which represent at risk, already achieved or a yellow to designate somewhere in between, take on a different meaning with only four months left to achieve, exceed or extend a goal.
Don’t get me wrong. I know we all haven’t exactly been coasting this summer. We know the world of biotech doesn’t sleep. Drug development is a long process, and patients are waiting. Overcoming the Midsummer’s Madness and managing the summertime challenges many biotech companies face is no small feat.
With the continued globalization of biotech, these challenges are reaching new heights. And not to ruin your vacation or anything, but I thought it might be worth mentioning some of the things and critical questions that may already be creeping into view. It might also help to know that you are not alone and that you and your team got this. For others this may serve as a reminder of some of the pitfalls that can befall biotech companies this time of year and what the key questions are to ask yourself and the team to manage through the madness and finish strong in 2024.
Clinical Trials
Are your clinical trials on track? Companies fortunate enough to have reached the clinical stage are asking this question. What has the impact of summer been on recruiting efforts and the ability to manage clinical trial participants? Or maybe you are nearing the clinic. Have you identified and reached out to the PIs and potential clinical trial sites? Do you have ample drug supply? What is the status of CMC in the summer, a time that can call for creative solutions?
Human beings have a tendency to become more lax when they are relaxing. And importantly, breaks from treatment or treatment protocols can literally make or break trials. There is no room for a missed dose, a scheduled follow-up visit or opportunities to bring new clinical sites on board. Keeping trial sites, CROs, PIs and patients engaged when schedules are disrupted by vacation is difficult and can be vacation killers. The ‘fill-in’ site coordinator or covering CRO trial manager may not be fully up to speed on all the details of the trial. Do they know who the sponsor is or how to contact the right person if questions arise?
Anticipating these things and keeping close ties with sites and CROs ahead of and during summer months is critical to the success of a trial. This is especially true for rare disease trials with so few patients or trials involving patients with numerous concomitant or life-threatening conditions. An adverse event or serious adverse event (SAE) that turns out NOT to be related to the drug may take a while to sort out. Keeping tight patient management and timely reporting intact no matter where folks are traveling is key to handling these well. What’s worse would be having an SAE that could have been avoided had someone been monitoring the patient more closely over the summer, or if the patient had known when and where to seek help earlier. Ensuring appropriate vacation coverage and renewing patient education efforts, including those that address potential areas for protocol deviation, is time and money well spent. Maintaining open, two-way communications with trial sites over the summer, or any holiday for that matter, keeps the trial intact and on track. I am once again reminded of how a poorly designed or executed clinical trial can fail a drug.
Clinical trials are becoming more global as companies seek to take advantage of potential accelerated development timelines. This is especially true of early-stage companies who need to conserve cash and facilitate rapid data generation. Nowadays it is common to conduct initial clinical trials in Australia, the United Kingdom, Germany or other select geographies to obtain a quick safety readout, gain important dosing information and guide patient selection for future studies. For initial SAD/MAD trials that also include patients, obtaining early signs of efficacy in addition to safety data serves many purposes including informing the design of Phase 2a trials and beyond. Australia has become a popular geography for conducting these early-stage trials. The process and approval for clinical trials can be quicker when compared to IND filings in the U.S. Hedging their bets has led many companies to pursue a parallel track by conducting initial trials ex-U.S. while advancing an IND filing. This can allow initial data from Phase 1 SAD/MAD trials conducted ex-U.S. to be incorporated into an IND submission, in many cases bolstering the filing.
CMC/Tech Ops
Biotechs operating on a global basis may experience a heightened Midsummer’s Madness that extends beyond employee vacations and clinical trial management challenges. Ex-U.S. vacations, which are typically more ‘off the grid’ than in the U.S., can have a significant impact on manufacturing timelines and drug supply chains. As the CEO of Lifordi Immunotherapeutics, an ADC company developing treatments for autoimmune and inflammatory diseases, there are three components to manufacture, multiple international CDMOs to manage, and complex supply chains to navigate. I can tell you that CDMO summer shutdowns are a real thing. Keeping ahead of schedule will help to maintain manufacturing efficiencies, ensure adequate supply and product quality, and meet development timelines. I am fortunate to have a great Tech Ops team at Lifordi who is on top of managing all the moving parts across the globe for making tox and clinical supply for us. We will have to support an evolving clinical development plan and to keep manufacturing off the critical path. The decision to pursue a much larger immune-mediated disease for our lead program versus a smaller, niche indication was not hindered by manufacturability or scalability. Instead, it was based on the large unmet need, the advantages of a unique ADC-based delivery platform, and a strong preclinical data package that supported this strategy.
Regulatory Submissions, Meetings and Feedback
How is the Briefing Book coming? Will you be able to take a breath when you have pressed the button to submit the Pre-IND or IND meeting request to FDA or a CTA to another regulatory agency? There is no ‘cruise control’ when the clock starts ticking upon submission. Preparations for a regulatory meeting are crucial and if this is happening during the summertime, you are definitely in ‘go mode’ regardless of the nice weather! Getting regulatory documents ready for submission in the summer months relies on pulling key members of the team together whether they are at the Lake, on the beach, in the mountains or along the coastline. The average time from submitting a meeting request to FDA and being granted a meeting date has recently accelerated so Briefing Books should be in final form before submitting the meeting request.
Investors, Analysts and Bankers and Board Members
“Can I stop by for an update”, said a banker as well as an analyst to me recently because they just happened to be in the neighborhood. Both were more than happy to meet anywhere at almost any time during their short visit to town. Despite the relative slowdown in the market, investors are still investing, bankers are still preparing and completing deals, and analysts continue to cover companies and the space. The banker made no bones about his trying to squeeze in as many meetings with clients and prospects over the next two weeks as possible before he takes a brief hiatus ahead of Labor Day.
Board members, too, want to stay abreast of a company’s progress over the summer. Keeping frequent communications alive and well over the summer is a winning strategy. A Midsummer’s Madness can reach higher levels if you are contemplating the next financing round in the near term. It is never too early to hone your strategy and share these thoughts with Board members. As a biotech operator as well as a VC, I understand the push and pull of these types of financing conversations, but they are worth having early and often. And should you forget, if even for a moment, that strong investor support is critical at any stage of development, you may find yourself participating in a virtual investor conference or an analyst day over the summer that includes a full day of one-on-one meetings. Just last week I was sitting in front of the computer in Zoom meetings during a bank conference wearing a dress shirt and a bathing suit to facilitate a quick dip in the lake during the lunch break. A Midsummer’s Madness is knowing that this is a prelude to the series of conferences that surface just after Labor Day and continue steadily throughout the back half of the year.
Employee Engagement
A Midsummer’s Madness would not be complete if it didn’t include ruminating about employee engagement. Recognizing that employee down time is much needed and well deserved to preserve a healthy work-life balance, we try to find that right mix of check ins on goals and milestones as well as Town Hall meetings to make sure things are generally on track.
How many Town Halls should we have? Should we check calendars to make sure that enough people can attend in person? Should we include a Zoom link in case people who ARE on vacation can call in if they want? But maybe then there is an expectation that they should call in, which is not the message you want to send necessarily.
What helps to keep a Midsummer’s Madness at bay is knowing that you have built an experienced and dedicated team who continue to deliver so that major timelines do not slip. It also comes from having the confidence that the company shares the same vision. At Lifordi, this is to develop therapies for patients with autoimmune and inflammatory diseases whose current options are limited by the safety concerns associated with existing treatments, particularly when they are used long term. We know the need is large and growing, and we embrace the mission.
Patients are Waiting
Patients living with life-altering and devastating diseases may take a vacation but they rarely, if ever, get a break from their disease. Each year when the Midsummer’s Madness kicks in, I remember that there is a method to the madness. It is keeping patients front and center. They are the reason that we keep going and why we remain committed to developing novel therapies that can improve their lives as well as those of their families and caregivers. This is why clinical trials must go on, regulatory agencies take action over the summer, and why investors, analysts, bankers, and Boards continue to hold us accountable for delivering on our goals. And so, we should counter another Midsummer’s Madness with a Midsummer’s Night Dream that we can make life better for the patients who are waiting and for those who will come after.
