Full Press Release Details
Biopharma Responds to COVID-19 Pandemic by Advancing TD-0903 to
Treat Hospitalized Patients with Acute Lung Injury
DUBLIN, IRELAND and SOUTH
SAN FRANCISCO, CA - APRIL 9, 2020 -- Theravance Biopharma, Inc. (NASDAQ: TBPH) ("Theravance Biopharma" or the "Company"),
a diversified biopharmaceutical company primarily focused on the discovery, development and commercialization of organ-selective
medicines, today announced that it is advancing TD-0903, a lung-selective nebulized Janus kinase inhibitor (JAKi) into clinical
development to assess its utility in preventing the cytokine storm associated with Acute Lung Injury (ALI) in patients hospitalized
due to COVID-19, with the ultimate goal of preventing progression to Acute Respiratory Distress Syndrome (ARDS).
the unprecedented healthcare challenges presented by the emergence of COVID-19, we have combined our immunology and respiratory
medicine expertise to accelerate development of our nebulized lung-selective JAK inhibitor, TD-0903. With great urgency, we have
redirected our program to treat the acute lung injury caused by COVID-19," said Rick E Winningham, Chief Executive Officer.
"We recognize how critical it is to help those suffering from shortness of breath and low oxygen levels, including those
who need intensive care and ventilation, to address the effects of profound lung hyperinflammation. TD-0903 could provide benefit
to hospitalized patients by preventing the progression of lung hyperinflammation and reducing the requirement for, or the duration
of, assisted ventilation. As a result, this could improve utilization of limited hospital critical care resources."
to be able to direct our resources and expertise towards helping to treat COVID-19," said Brett Haumann, M.D. Chief
Medical Officer. "Janus kinase inhibitors have the potential to inhibit a broad
set of immune-modulatory pathways that could prove to be effective in dampening the abnormal
immune response that occurs in the lungs of some patients. The nebulized formulation of our lung-selective inhaled JAK inhibitor
will allow TD-0903 to be administered directly to the lung in a number of hospitalized settings, including patients who can breathe
unaided in the ward, as well as in the ICU setting in patients who require non-invasive or mechanical ventilation. If our initial
CTA submission for this study in healthy volunteers is approved and the study is successful, we intend to study TD-0903 in COVID-19
patients in the very near future. We are proud of the tremendous efforts of the global team of Theravance Biopharma scientists
and physicians that has enabled us to rapidly progress TD-0903, and we are grateful for their collaboration and dedication to continue
TD-0903 is a lung-selective,
nebulized pan-JAK inhibitor that was discovered and developed at Theravance Biopharma. TD-0903 has been shown in experimental murine
models to have potent, broad inhibition of JAK-STAT signaling in the airways following challenges with multiple cytokines. By its
mechanism, TD-0903 has the potential to block release of cytokines and chemokines that may be associated with acute lung injury
and the initiation of a cytokine storm syndrome. Preclinical studies suggest that TD-0903 has a very high lung:plasma ratio and
rapid metabolic clearance resulting in low systemic exposure, compatible with its lung selectivity. TD 0903 is administered
via nebulized inhalation solution, which further enhances its lung selectivity. Preclinical pharmacodynamic studies indicate that
TD-0903 has an extended duration of action that should enable once or twice daily dosing in humans.
As disclosed initially
at Theravance Biopharma's December 2018 Research and Development Day, the Company indicated the initial clinical application
of TD-0903 would be to explore its utility in preventing/delaying graft rejection among individuals receiving lung transplantation.
Although this is still a potential clinical application for TD-0903, in response to the current COVID-19 pandemic, the Company
has prioritized activities toward assessing the potential for TD-0903 to treat hospitalized COVID-19 patients who become short
of breath and whose blood oxygen levels begin to drop. These patients appear to be at increased risk of respiratory complications
including Acute Lung Injury (ALI) and Acute Respiratory Distress Syndrome (ARDS). They may also require prolonged hospitalization,
continuous oxygen and, in the most severe cases, admission to ICU to assist their breathing with non-invasive and/or mechanical
ventilation. Treatment with JAK inhibition is recognized as an important anti-inflammatory mechanism to potentially reduce the
hyperinflammation seen in hospitalized COVID-19 patients who develop ALI and ARDS.1
Upon review and approval
of the initial CTA, the Company is planning to initiate a Phase 1 study this month in the United Kingdom (UK), starting with single-
and multiple-ascending doses in healthy volunteers to assess safety. Upon regulatory review and approval, the program will then
move to a nested Phase 2 study in hospitalized patients with COVID-19. The Phase 2 study will consist of two parts. The first part
will assess the safety, tolerability and clinical response to treatment in sequential ascending dose cohorts of COVID-19 patients
in the UK. This part of the study will not be formally powered for efficacy but will inform the selection of dose(s) for the second
part. The second part of the Phase 2 study will be a larger, multi-center study conducted at hospital-based clinical sites in the
UK, and potentially other clinical sites in the European Union and United States. Both of the latter territories would join the
Phase 2 study program following review and approval of the relevant regulatory filings required by the European Medicines Authority
(EMA) and Food and Drug Administration (FDA). Further details on the program, including more on Phase 1 and Phase 2 studies will
be provided once these studies have been approved by the appropriate regulatory and ethics review authorities.
Theravance Biopharma's efforts leverage years of experience
in developing lung-selective medicines to treat respiratory disease.
1 The Lancet, March 13,
2020, "COVID-19: consider cytokine storm syndromes and immunosuppression" Mehta, McAuley, Brown, Sanchez, Tattersall,
About the Inhaled JAK
JAK inhibitors function
by inhibiting the activity of one or more of the Janus kinase family of enzymes (JAK1, JAK2, JAK3, TYK2) that play a key role in
cytokine signaling. Inhibiting these JAK enzymes interferes with the JAK/STAT signaling pathway and, in turn, modulates the activity
of a wide range of pro-inflammatory cytokines. Limiting JAK inhibition to the lung is expected to improve therapeutic index relative
to systemic inhibition. Thus, inhaled JAK inhibitors with lung-restricted exposure are of high interest as potential treatments
for respiratory illness.
TD-8236 is the Company's
most advanced investigational pan-Janus kinase (JAK) inhibitor currently designed for delivery to the lungs using a dry powder
inhaler (DPI). Similar to TD-0903, TD-8236 is a lung-selective agent designed to inhibit the JAK family of enzymes in lung tissue
with limited systemic exposure. An extensive set of preclinical pharmacological studies and toxicological studies support its current
clinical development in the primary indication of moderate to severe asthma. Insights from the ongoing clinical development of
TD-8236 DPI are informing the Company's confidence to bring TD-0903 forward for the treatment of COVID-19 acute lung injury.
In addition, Theravance
Biopharma is currently assessing the impact of the COVID-19 pandemic on its operations, including on the commercial operations
associated with YUPELRI (revefenacin inhalation solution) and on the conduct of its clinical development programs for TD-1473,
ampreloxetine and TD 8236. The situation continues to evolve as the pandemic's effects are felt around the world. The
Company has implemented a comprehensive business continuity plan to support its performance, and it remains well capitalized to
advance the company despite the obstacles presented by the current environment. The Company will provide further program updates
during its Q1 financial results and business update call in early May 2020.
Conference Call and Live Webcast Today at 8:00 a.m. ET
Theravance Biopharma will hold a conference call and live webcast
accompanied by slides today at 8:00 a.m. ET (5:00 a.m. PT / 1:00 p.m. GMT). To participate in the live call by telephone,
please dial (855) 296-9648 from the U.S., or (920) 663-6266 for international callers and use the confirmation code 5076939.
Those interested in listening to the conference call live via the internet may do so by visiting Theravance Biopharma's website
at www.theravance.com, under the Investor Relations section, Presentations and Events.
A replay of the conference call will be available on Theravance
Biopharma's website for 30 days through May 9, 2020. An audio replay will also be available through 11:00 a.m. ET on April 16,
2020 by dialing (855) 859-2056 from the U.S., or (404) 537-3406 for international callers, and then entering confirmation code
About Theravance Biopharma
Theravance Biopharma, Inc. ("Theravance Biopharma")
is a diversified biopharmaceutical company primarily focused on the discovery, development and commercialization of organ-selective
Our purpose is to create transformational medicines to improve
the lives of patients suffering from serious illnesses. Our research is focused in the areas of inflammation and immunology.
In pursuit of our purpose, we apply insights and innovation
at each stage of our business and utilize our internal capabilities and those of partners around the world. We apply organ-selective
expertise to biologically compelling targets to discover and develop medicines designed to treat underserved localized diseases
and to limit systemic exposure, in order to maximize patient benefit and minimize risk.
These efforts leverage years of experience in developing lung-selective
medicines to treat respiratory disease, including FDA-approved YUPELRI (revefenacin) inhalation solution indicated for the
maintenance treatment of patients with chronic obstructive pulmonary disease (COPD). Our pipeline of internally discovered programs
is targeted to address significant patient needs.
We have an economic interest in potential future payments from