Venture cash is set to remain plentiful for drug developers this year, and the steady flow of these start-ups onto the highly receptive public markets is showing no sign of abating. This generously lubricated financing cycle is also producing faster exit times: the median time from the establishment of a venture-backed biotech start-up to IPO shrank to a little over five years in 2020, the speediest year in at least the past five. A flotation is not an immediate exit for private investors, of course, although huge enthusiasm for biopharma stocks means that funds are probably able to sell on their holdings pretty easily right now. This facilitates a swifter return of capital to the venture firm’s own limited partners, who are thus happy to invest in the next fundraising – and the cycle continues. It is notable that time to M&A has not markedly quickened over this period, which only reinforces the importance of buoyant equity markets to the venture world’s ongoing boom.
Shares of Signify Health Inc jumped more than 33% in their stock market debut on Thursday, giving the technology-based healthcare provider a market capitalization of $7.12 billion.
Shares opened at $32, well above their raised initial public offering price of $24 apiece. The price range was initially set at between $20 and $21 per share.
The IPO raised about $564 million through the sale of 23.5 million shares.
Healthcare companies going public were among the key drivers of the IPO boom in 2020, PricewaterhouseCoopers said in a recent report, and 2021 is poised to be another bumper year for new offerings.
In another blockbuster debut on Thursday, shares of dating app operator Bumble Inc were set for a near 47% jump.
Signify was founded in 2017 through the merger of CenseoHealth and Advance Health, after the healthcare companies went through a recapitalization spearheaded by private equity firm New Mountain Capital.
The Dallas-based company offers in-home healthcare services, and its customers include healthcare plans, governments, employers and physician organizations.
The company serves 47 Medicare Advantage health plans, which provide benefits under the U.S. government’s health insurance program for the elderly through a private insurer, Signify had disclosed in its IPO filing.
Goldman Sachs, J.P. Morgan, Barclays and Deutsche Bank Securities are among the underwriters of the IPO.
The Cuomo administration has quietly set up 19 “COVID-only” nursing homes throughout the state to treat patients recovering from the killer bug who are discharged from hospitals.
State Health Commissioner Howard Zucker revealed the establishment of the coronavirus-only nursing homes in a 16-page letter sent to the state Legislature Wednesday, which was his response to a series of questions submitted by lawmakers who chair committees overseeing nursing homes.
Gov. Andrew Cuomo and his health department came under fierce criticism last spring — during the worst of the COVID-19 outbreak — when thousands of recovering coronavirus patients were released from hospitals and sent to nursing homes.
Some nursing home operators claimed a March 25 state Health Department directive pressured them to admit or readmit COVID-19 patients at a time when they were already overwhelmed by the outbreak. At the time, nursing homes were not allowed to test new admissions for COVID-19, had inadequate personal protective equipment and suffered from staffing shortages.
Nursing home operators complained they were told they could not transfer sick COVID-19 patients to the temporary state Javits Center hospital or the United States Navy’s Comfort hospital ship which then-President Trump dispatched to New York harbor to help treat sick patients during the pandemic.
“Starting in November the Department launched an effort to establish COVID-only nursing homes…The homes were established to allow the transfer of MEDICALLY STABLE, BUT persistently positive COVID-19 nursing home eligible patients from Article 28 hospitals to these nursing homes to further their recovery prior to discharge to home or another nursing home,” Zucker said in his response to legislators.
Zucker said there are 19 COVID-only nursing home sites scattered across all regions of the state, containing a total of 1,941 beds “to meet the needs of this special population.” He did not specify which nursing homes are used as COVID-only facilities.
Last spring there were only a handful of COVID-only nursing facilities.
In the letter, Zucker said 13,297 nursing home residents have died from COVID-19. The number jumps to 15,049 when including fatalities from other long-term care facilities such as assisting living and adult daycare centers.
Zucker also said the state spent more than $12 billion to address the COVID-19 pandemic in nursing homes and hospitals, mostly aid provided by the federal government. Nearly $9.2 billion went to hospitals and $520 million to nursing homes.
The health commissioner released the information to the Legislature after a tense meeting with lawmakers, who had accused him and Cuomo of “stonewalling” them for months by failing to disclose the complete count of nursing home residents who died from COVID-19. Others had accused Zucker of being a Cuomo ”puppet” and liar.”
The meeting was also attended by top Cuomo aides, including secretary to the governor Melissa DeRosa and budget director Rob Mujica.
Team Cuomo’s meeting with lawmakers comes on the heels of a stinging investigative report by state Attorney General Letitia James that found the administration had misled the public by undercounting COVID-19 nursing home resident deaths by 50 percent. State health officials only counted nursing home residents who died in those facilities, but excluded thousands who died in hospitals.
“I don’t think the meeting was particularly productive. I don’t think we got the answers to our questions but the governor’s people have said they would welcome getting back to them with follow up questions and we plan to do that and hopefully that will bring out more information,” said Assembly Health Committee Chairman Richard Gottfried (D-Manhattan).
“The information that we’ve all been looking for about the number of deaths to nursing home residents who died in hospitals is still not at all clear and the answers to a lot of other questions about visiting policies or other things were just statements like, `we’re working on it.”’
Assemblyman Ron Kim (D-Queens), the aging committee chairman whose uncle died of COVID-19 in a nursing home last year said of the meeting, “There were some heated exchanges at the beginning. Some members felt like they put their neck on the line and stood by the administration, and they felt betrayed with how they were treated.”
The senators who attended the meeting released Zucker’s 16-page letter, which was a response to a series of questions they submitted to him last year following a stormy legislative hearing on nursing homes. They had grilled Zucker, who testified for two hours.
“While we appreciate that our letter from August 2020 has finally been answered and, two weeks ago, nursing home data was released, it is unacceptable that it took so long,” said the statement from Senate Health Committee Chairman Gustavo Rivera (D-Bronx), Investigations Committee Chairman James Skoufis (D-Orange) and Aging Committee Chairwoman Rachel May.
“Our original letter was sent following 40 hours of hearing testimony and after so many legislators, families, and members of the public demanded answers.”
Meanwhile the Empire Center for Public Policy, which won a Freedom of Information Lawsuit lawsuit to force the Cuomo administration to release more details about COVID-19 nursing home deaths, said the belated information received Wednesday from the Health Department was insufficient. A judge ruled team Cuomo illegally withheld the data and ordered its release.
Despite considerable progress, genetic medicine is still mostly limited to the treatment of rare diseases. Developers are racing to broaden its reach, with the latest entrant debuting Thursday, supported by one of the world's largest pharmaceutical companies.
The startup, Ensoma Therapeutics, has emerged with $70 million in Series A financing and a wide-ranging collaboration with Takeda that includes up to five experimental programs. The fundraising was led by venture capital firm 5AM Ventures as well as a half dozen other investors.
Ensoma's goal is highly ambitious. The company says it will use an unorthodox method to turn gene modifying medicines normally made through a complex, laborious process into "off-the-shelf" products. By doing so, Ensoma aims to develop treatments for common as well as rare diseases, and make them available beyond specialized centers.
"The intent of our therapy is to be able to deliver this in an outpatient setting, anywhere, even in a doctor's office or clinic," said Ensoma's executive chair Paula Soteropoulos, an industry veteran who recently ran Akcea Therapeutics.
Paula Soteropoulos, Ensoma Therapeutics
Courtesy of Ensoma Therapeutics
Over the past several years, genetic medicines have shown great promise in treating a handful of rare diseases. Two such medicines, Luxturna and Zolgensma, are approved in the U.S. for eye and neuromuscular conditions, respectively. Others may soon emerge as treatment options for rare blood disorders like sickle cell disease and beta thalassemia.
Many of the treatments rely on modified viruses to shuttle genetic instructions into the body's cells — delivery vehicles repurposed from nature that come with strengths as well as weaknesses. One example, adeno-associated viruses, or AAVs, can be easily administered via infusion, have proven safe in clinical testing and are the backbone of a wide range of gene therapies.
But AAVs can only carry a small amount of genetic cargo and are sometimes shut down by the body's defenses. The DNA they transport also doesn't easily integrate into a target cell's genome, meaning the effects of AAV-based treatment may wane in cells that frequently divide.
Another commonly used option, lentiviruses, do integrate and can be used for many different tasks, such as engineering stem cells to correct or work around the defective DNA that drives certain blood diseases.
Yet lentiviruses also have limited packaging capacity. And because they readily integrate into cellular DNA, there's greater risk of erroneously triggering cancer-causing mutations, as occurred in an early 2000s gene therapy trial in France that used a different type of virus. So scientists typically make such treatments through a tightly controlled process in which cells are first extracted from the body, then precisely modified using lentiviruses in a laboratory.
These "viral vectors" have enabled gene therapy to come of age after decades of stop-and-start scientific research. But their limitations have become increasingly well understood, which is why a number of companies have emerged aiming to improve the technology and widen its impact.
The concept behind Ensoma, for instance, is to deliver a larger, and more varied, payload of gene-modifying tools than its peers have been able to do with existing viral vectors. The company is taking an adenovirus, stripping its viral genome, and using the excess space — some six or seven times the capacity of an AAV — to cram in functional genes or even the means to modify them.
Ensoma says its platform can deliver into cells genome editing technology like CRISPR/Cas9 or zinc finger nucleases, or sets of instructions for how much of a gene to express. "We can fit it all," said Kush Parmar, founding CEO and a managing partner at 5AM Ventures.
Kush Parmar, Ensoma Therapeutics
Courtesy of Ensoma Therapeutics
Preclinical research underlying Ensoma's approach, published in the Journal of Clinical Investigation in 2019, gave a glimpse into how the approach could be used to design a treatment for beta-thalassemia. In tests in mice, researchers used a drug to move hematopoietic stem cells from the bone marrow into the blood, where they were infected by an infused, genetically engineered adenovirus. The cells then returned to the bone marrow, where they persisted and produced corrected red blood cells.
Ensoma aims to use its method to make genetic medicines for a variety of rare and common diseases. The hope is these medicines could be less cumbersome than gene-based treatments that rely on outside-the-body cellular engineering, such as the ones Bluebird Bio, CRISPR Therapeutics and others are now testing for beta-thalassemia and sickle cell disease.
Ensoma also expects to be able to avoid the "pre-conditioning" chemotherapy regimens used by Bluebird and CRISPR to prepare patients to receive their cell-based medicines. While familiar to transplant specialists, the regimen can come with side effects.
"This sounds really compelling," said Luk Vandenberghe, the director of the Grousbeck Gene Therapy Center at Massachusetts Eye and Ear. Vandenberghe, who isn't involved with Ensoma, added that the "complexity" of other approaches "often limits the reach of these therapies, even in the West."
Ensoma's method, he said, could be "really quite impactful for diseases like sickle cell" and potentially as an alternative to the logistically challenging cancer cell therapies that have come to market.
Soteropoulos, the company's chair, noted the potential advantages in convenience allows Ensoma to think about using gene therapy to address infectious diseases or autoimmune conditions.
Before that can happen, though, Ensoma has much to prove. Adenoviruses have a checkered past in gene therapy. Though they were among the first delivery tools used in clinical tests, safety concerns — most notably the death of a teenage study volunteer two decades ago — curtailed their use, ushering in the emergence of AAVs.
"Innate immunity is indeed the concern that adenovirus therapies have to address," Vandenberghe said. The challenge is to find a "good therapeutic window to avoid the issues seen in the past." Still, he noted that "the preclinical data in the literature looks promising that [Ensoma] will find such a window."
Indeed, Parmar said the viruses Ensoma is using are "gutless" and have "extremely low to negligible pre-existing immunity."
"These are not the adenoviruses of 20 years ago," he said.
That will have to be shown in animal studies and, should those look positive, human trials. Soteropoulos said the "fastest path" to clinical tests is to produce inside-the-body versions of treatments that have already shown promise via ex vivo approaches. She noted, though, that it's too early to say how far the company is from its first tests or what diseases it will initially target.
Ensoma could receive up to $100 million in upfront and near-term payments from Takeda. The startup could also earn as much $1.25 billion from the deal later on, though that cash isn't guaranteed and may not materialize.
While Takeda may seem an unusual partner, the Japanese drugmaker has been making a major push into cell and gene therapy, hoping to improve on the current crop of treatments. Its research programs, however, remain at a comparatively early stage.
Rite Aid (NYSE: RAD) is expanding no-charge COVID-19 self-swab testing to all drive-through locations, with 441 additional sites opening Friday, February 12, through its partnership with the U.S. Department of Health and Human Services (HHS).
The new testing sites will increase Rite Aid's capacity for COVID-19 testing services in California, Connecticut, Delaware, Idaho, Maryland, Michigan, New Hampshire, Ohio, Oregon, Virginia and Washington.
Like Rite Aid's existing drive-through testing sites, the new locations will utilize PCR, simple self-swab nasal tests overseen by Rite Aid pharmacists and will operate Monday through Friday 10 a.m. - 8 p.m. and Saturday and Sunday 10 a.m. - 5 p.m. Rite Aid's COVID-19 nasal tests are available for all individuals four years of age and older, regardless if they are experiencing virus symptoms, in accordance with the Centers for Disease Control and Prevention (CDC) guidance.
At all testing locations, customers are required to pre-register online at www.riteaid.com in order to schedule a time slot for testing. Individuals ages 4-17 may access testing with parent or legal guardian consent. Additionally, a parent or legal guardian must be in attendance and bring their photo ID to the testing appointment with the minor.
Now operating more than 1,200 testing sites across 16 states, Rite Aid is expanding access to essential testing services across more communities while ensuring the safety of in-store customers by offering testing exclusively via the drive-through. A complete list of Rite Aid's COVID-19 testing sites can also be found at www.riteaid.com.
Celsion Corporation (NASDAQ: CLSN), an oncology drug development company, today announced that Michael H. Tardugno, the company’s chairman, president and chief executive officer, issued a letter to stockholders providing:
Further details on the Company’s vaccine initiative using its PLACCINE DNA vaccine platform technology for preventing or treating infectious agents that have the potential for global pandemics, including the SARS-CoV-2 virus and its variations;
Expectations for clinical development programs with GEN-1, the company’s DNA-mediated IL-12 immunotherapy currently in Phase II development for the treatment of advanced ovarian cancer;
An update on the status of the Phase III OPTIMA Study with ThermoDox® plus radiofrequency ablation (RFA) in patients newly diagnosed with primary liver cancer, or hepatocellular carcinoma (HCC) and the decision to stop following patients in the Study; and
A review of the company’s strong financial condition and three-year operating runway.
The full text of the letter follows.
To My Fellow Stockholders:
Celsion enjoys a broad base of technologies and competencies. Although 2020 was a challenging year in terms of the OPTIMA Study findings and the impact of COVID-19, we are, in fact, positioned for a future of broader development and exciting prospects. My message to you today is that a single disappointing study, OPTIMA, is not going to diminish the prospects of Celsion and its potential to bring exciting medicines to market.
Let me explain why, starting with TheraPlas and its adaptation to the PLACCINE platform.
Through its first investigational product GEN-1, Celsion’s TheraPlas technology has demonstrated it can safely and effectively deliver and activate a DNA plasmid in patients. More than 90 patients have been treated in our oncology program with results demonstrating excellent safety, and with data clearly showing the activation of an immune response. We now believe that an adaption of the TheraPlas technology can do the same as a much-needed vaccine for the near future. We are calling this version of our proprietary plasmid and DNA delivery technology the PLACCINE platform. PLACCINE is the subject of our recently filed provisional patent that was announced on January 28, 2021.
Focus on Immunotherapies and Infectious Disease Vaccines
Future vaccine technology will need to address viral mutations and the challenges of efficient manufacturing, distribution, and storage. We believe an adaptation of our TheraPlas technology, PLACCINE, has the potential to meet these challenges, and perhaps more. Our approach is described in our provisional patent filing and is summarized as a DNA vaccine technology platform characterized by a single plasmid DNA with multiple coding regions. The plasmid vector is designed to express multiple pathogen antigens along with a potent immune modifier. It is delivered via a synthetic delivery system and has the potential to be easily modified to create vaccines against a multitude of infectious diseases, addressing:
Viral Mutations: PLACCINE may offer broad-spectrum and mutational resistance (variants) by targeting multiple antigens on a single plasmid vector.
Enhanced Efficacy: The potent immune modifier IL-12 may improve humoral and cellular responses to viral antigens and can be incorporated in the plasmid.
Durable Efficacy: PLACCINE delivers a DNA plasmid-based antigen that can result in durable antigen exposure and a robust vaccine response to viral antigens.
Storage & Distribution: PLACCINE allows for stability that is compatible with manageable vaccine storage and distribution.
Simple Dosing & Administration: PLACCINE is a synthetic delivery system that should require a simple injection that does not require viruses or special equipment to deliver its payload.
We are conducting preliminary research associated with our recently announced proprietary DNA vaccine platform provisional patent filing. At the same time, we are redoubling our efforts and R&D resources in the immuno-oncology program.
GEN-1, OVATION 2 and Immunotherapy
The Phase II OVATION 2 Study with GEN-1, our DNA-mediated IL-12 immunotherapy, is the first product designed using the Company’s TheraPlas platform technology. The OVATION 2 Study combines GEN-1 with standard-of-care neoadjuvant chemotherapy (NACT) in patients newly diagnosed with Stage III/IV ovarian cancer. NACT is designed to shrink the cancer as much as possible for optimal surgical removal after three cycles of chemotherapy. Following NACT and eight weekly cycles of GEN-1, patients undergo interval debulking surgery, which is then followed by three adjuvant cycles of chemotherapy and up to nine additional weekly GEN-1 treatments. The goal of our treatment strategy is to delay progression and improve overall survival (OS). The OVATION 2 Study is an open-label, 1-to-1 randomized trial, 80% powered to show the equivalent of a 33% improvement in progression-free survival (PFS) (HR=0.75), the primary endpoint, when comparing the treatment arm (standard-of-care + GEN-1) with the control arm (standard-of-care alone).
We have enrolled one-third of the study patients with advanced ovarian cancer at 19 active centers. I am proud to say that by the end of the first quarter, we expect that all 25 clinical sites in the U.S. and Canada will be up and running. This has been no easy task given the impact the COVID -19 pandemic has had on hospital resources and personnel availability. Patient enrollment is expected to be completed sometime during the second half of 2021, unless the pandemic continues to interfere with clinical trials. We expect to release overall response rate (ORR) and surgical resection scores as they become available during the course of 2021. The study’s primary endpoint is expected to be announced during the fourth quarter of 2022.
As a reminder, based on favorable safety data from 15 randomized patients in the Phase I portion of the OVATION 2 Study, in June 2020 the Data Safety Monitoring Board (DSMB) recommended that the Phase II portion proceed with the dose of 100 mg/m2. Of these 15 patients, nine were treated with GEN-1 at a dose of 100 mg/m² plus NACT and six were treated with NACT only. All 15 had successful resections of their tumors, with eight out of nine patients (88%) in the GEN-1 treatment arm having an R0 resection, which indicates a microscopically margin-negative resection in which no gross or microscopic tumor remains in the tumor bed. In comparison, only three out of six patients (50%) in the standard-of-care arm had an R0 resection. Additionally, a manuscript detailing the results of our Phase 1 OVATION 1 Study has been submitted for publication. Translational and clinical data from this dose-escalating study support GEN-1’s continued development. I look forward to announcing acceptance of this manuscript by a peer-reviewed publication in the near future.
OPTIMA Study Analyses and ThermoDox® Status
Since the surprising and incredibly disappointing second interim analysis results of the Phase III OPTIMA Study in HCC announced on July 9, 2020, in which the independent Data Monitoring Committee (DMC) found that the interim findings suggested futility, we have continued to follow patients for OS. Independent analyses conducted by a global biometrics contract research organization, and by the National Institutes of Health (NIH), did not find any evidence of significance or factors that would justify continuing to follow patients for OS. Therefore, the Company will be notifying all clinical sites to discontinue following patients. The OPTIMA Study database of 556 patients will now be frozen at 185 patient deaths.
As a reminder, we had previously stated that it would be highly unlikely the DMC’s recommendation would be reversed by subsequent data analyses. And while the analyses did identify certain patient subgroups that appear to have had a clinical benefit, we concluded that it would not be in our best interest to pursue these retrospective findings as the regulatory hurdles supporting further discussion will be significant.
A single disappointing study does not mean an end to the future of ThermoDox®. Celsion continues working closely and supporting investigations by others throughout the world in breast cancer, pancreatic cancer and in solid tumors in children. Following inquiries from the NIH, we intend to renew our Cooperative Research and Development Agreement (CRADA) with the Institute at a nominal cost, one goal of which is to pursue their interest in a study of ThermoDox® to treat patients with bladder cancer. Importantly, Celsion is developing a business model to support these investigator-sponsored studies in a manner that will not interfere with the Company’s focus on our GEN-1 programs and our vaccine development initiative.
Strong Balance Sheet
Celsion is fortunate to be in an excellent financial position to fund the achievement of our near-term milestones, with an anticipated cash runway of nearly three years. Including the $35 million equity financing announced in January 2021, we currently have approximately $58 million in cash and cash equivalents on our balance sheet. In conjunction with the registered direct common stock only financing in January 2021, we terminated our Common Stock Purchase Agreement with Lincoln Park Capital. During the third quarter of 2020, the Company restructured its venture debt facility with Horizon Technology Finance Corporation, thereby reducing our outstanding debt obligation from $10 million to $5 million.
Furthermore, we were pleased in early February to have received written notice from the Listing Qualifications Staff of The Nasdaq Stock Market notifying us that we had regained compliance with the minimum bid price listing requirement set forth under Listing Rule 5550(a)(2). As such, shares of our common stock continue to trade on The Nasdaq Stock Market without interruption.
In Conclusion
While 2020 brought the challenges of navigating the COVID-19 pandemic, we are heartened by the promise of our platform technologies to improve the lives of patients. We look forward to an active and potentially highly rewarding future, and to updating you on our progress.
On behalf of all our employees, I thank our stockholders for their continued support.
Sincerely,
Michael H. Tardugno Chairman, President and Chief Executive Officer February 11, 2021
