Takeda Announces Exclusive License and Option Agreement with Natrogen for Development of Natura-alpha for Inflammatory Bowel Disease

OSAKA, Japan & DEERFIELD, Ill. & NEW YORK--Takeda Pharmaceutical Company Limited ("Takeda") and Natrogen Therapeutics International, Inc. ("Natrogen") jointly announced today an agreement whereby Takeda will acquire an exclusive license to develop Natrogen's Natura-alpha compound as well as an option to acquire Natrogen. Natura-alpha is a synthetic small molecule oral compound that is believed to inhibit pro-inflammatory cytokine expression, which may help to reduce gastrointestinal inflammation. Natura-alpha is currently in Phase 2 development for the treatment of ulcerative colitis (UC).

"Today's announcement reinforces Takeda's continued commitment toward addressing the needs of patients with gastrointestinal diseases," said Asit Parikh, M.D., Ph.D., vice president, general medicine, Takeda. "Natura-alpha is a strategic fit with our gastrointestinal portfolio, which also includes vedolizumab, Takeda's investigational monoclonal antibody for the treatment of adults with moderately to severely active UC and Crohn's disease."

The principal activity of Natrogen Therapeutics International has been to develop Natura-alpha, a small molecule oral compound that has been the subject of a Phase 2 Clinical Trial exploring efficacy and safety in patients with ulcerative colitis.

"Natrogen's strategy has been to demonstrate the drug's efficacy and safety in clinical trials and then identify a major pharmaceutical company that has the expertise, commitment and financial resources to complete the regulatory process and bring the drug to market. We found the perfect partner, Takeda, a major research-based company that has a global presence in the area of gastrointestinal disease," said Louis Wang, M.D., president and chief scientist.

Under the terms of the agreement, Natrogen grants Takeda an exclusive license for worldwide development of Natura-alpha in all indications, and an option to acquire Natrogen. In return, Natrogen will receive an up-front payment and potential future payments upon the exercise of Takeda's option to acquire Natrogen, including a payment upon closing of the option to acquire Natrogen and potential post-closing contingent payments upon achievement of certain regulatory and sales milestones. Takeda will fund and execute all additional clinical development.

Leerink Swann LLC served as the exclusive financial advisor and Covington & Burling LLP served as the legal advisor for the transaction for Natrogen. Ropes & Gray LLP served as legal advisor for the transaction for Takeda.

About Natura-alpha

Natura-alpha is a synthetic small molecule that is believed to inhibit expression of pro-inflammatory cytokines (Interleukin-1, Interleukin-6 and tumor necrosis factor), which can increase inflammation and act to make diseases worse. Natura-alpha is thought to block inflammatory cytokines, while stimulating the production of cytokine IL-10 that can repress pro-inflammatory responses and limit unnecessary tissue disruptions caused by inflammation.

About ulcerative colitis and Crohn's disease

Ulcerative colitis (UC) and Crohn's disease (CD) are the two most common forms of inflammatory bowel disease (IBD), which is marked by inflammation in the GI tract. UC impacts the large intestine only, which includes the colon and the rectum. The most common symptoms of UC include abdominal discomfort and blood or pus in diarrhea. CD can impact any part of the digestive tract and common symptoms may include abdominal pain, diarrhea, rectal bleeding, weight loss, and fever. There is no known cause for UC or CD, although many researchers believe that the interaction between genes, the body's immune system, and environmental factors may play a role. The aim of UC and CD treatments is to induce and maintain remission, or achieve extended periods of time when patients do not experience symptoms.

About Takeda Pharmaceutical Company Limited

Located in Osaka, Japan, Takeda is a research-based global company with its main focus on pharmaceuticals. As the largest pharmaceutical company in Japan and one of the global leaders of the industry, Takeda is committed to strive towards better health for patients worldwide through leading innovation in medicine. Additional information about Takeda is available through its corporate website, www.takeda.com.

About Natrogen Therapeutics International, Inc.

Based in New York City, Natrogen Therapeutics International, Inc. is a midstage (through a phase-2 trial) biotechnology firm that uses cutting edge science to research and develop innovative therapeutics for three classes of diseases: immuno-inflamatory diseases, dermatological conditions and cancer.

Forward-Looking Statements

This press release contains "forward-looking statements." Forward-looking statements include all statements other than statements of historical fact, including plans, strategies and expectations for the future, statements regarding the expected timing of filings and approvals relating to the transaction, the expected timing of the completion of the transaction, the ability to complete the transaction or to satisfy the various closing conditions, future revenues and profitability from or growth or any assumptions underlying any of the foregoing. Statements made in the future tense, and words such as "anticipate," "expect," "project," "continue," "believe," "plan," "estimate," "pro forma," "intend," "potential," "target," "forecast," "guidance," "outlook," "seek," "assume," "will," "may," "should," and similar expressions are intended to qualify as forward-looking statements. Forward-looking statements are based on estimates and assumptions made by management that are believed to be reasonable, though they are inherently uncertain and difficult to predict. Investors and security holders are cautioned not to place undue reliance on these forward-looking statements.

Forward-looking statements involve risks and uncertainties that could cause actual results or experience to differ materially from that expressed or implied by the forward-looking statements. Some of these risks and uncertainties include, but are not limited to: required regulatory approvals for the transaction may not be obtained in a timely manner, if at all; the conditions to closing of the transaction may not be satisfied; the transaction may not be consummated including Takeda's decision not to exercise its option to acquire Natrogen; the anticipated benefits of the transaction may not be realized; the transaction could disrupt relationships with employees, licensees, customers and other business partners or governmental entities; future sales could be adversely affected by competition or other factors; and integration costs may exceed current expectations. In addition, the combined business could be adversely affected by industry, economic or political conditions outside of Natrogen's or Takeda's control, including general economic conditions in Japan, the United States and worldwide; competitive pressures and developments; applicable laws and regulations; the success or failure of product development programs; actions of regulatory authorities and the timing thereof; changes in exchange rates; and claims or concerns regarding the safety or efficacy of marketed products or product candidates in development.

The forward-looking statements contained in this press release speak only as of the date of this press release, and neither Natrogen nor Takeda undertake any obligation to revise or update any forward-looking statements to reflect new information, future events or circumstances after the date of the forward-looking statement. If one or more of these statements is updated or corrected, investors and others should not conclude that additional updates or corrections will be made.