Post Operative Tissue Fibrosis.
TTX333
Surgeons and patients will tell you it is a serious quality-of-life issue that affects millions of post-surgical patients with no effective solution (1), costs the healthcare system billions of dollars annually, and cutting away or taking down existing scar tissue from previous surgery, prolongs and complicates procedures (i.e. 1 in 5 risk of inadvertent bowel injury requiring re-operations).
- Surgical adhesions are often more dangerous than ones that spontaneously develop and can be life-threatening and cause significant patient morbidity
- Cost estimates exceed $5B annually just in the US
- Adhesion-related abdominal pain is one of the most common admissions to the ER in the US; up to 1/3 of these patients are known to use opioids to manage pain (2-5)
Temple believes postoperative tissue fibrosis is a serious quality-of-life issue, and we seek to address this condition using top-notch science.
- Greater complication cost than infection/hemorrhage
- According to Cochrane Review (2020)-No effective therapies currently approved (1)
- They can form anywhere but frequently arise as a result of surgery. These surgical adhesions are often more dangerous than ones that spontaneously develop and can be life-threatening.
- Cost estimates exceed $5B annually just in the US
- One of the most common admissions to the ER in the US–Adhesion related abdominal pain, which is also associated with high opioid use (2-5)
Tissue fibrosis refers to growths of fibrous connective tissue that join surfaces not normally connected within the body. They can form anywhere, but frequently arise as a result of surgery. These surgical adhesions are often more dangerous than ones that spontaneously develop and can be life-threatening.
Tissue fibrosis resulting from abdominal and pelvic surgery commonly causes chronic pain, bowel obstruction, and infertility in women and is the number one cause of post-surgical complications for these procedures.
90%
of pelvic and abdominal surgeries result in fibrosis.
No drug treatments currently exist for fibrosis, and surgeries attempting to reverse its effects worsen the condition about 70 percent of the time.
Currently, the most commonly used method for preventing postoperative adhesion is the use of barrier materials, which are thin films placed strategically around the surgical site to physically block fibrotic tissue from joining tissues or organs. These products are, at best, only about 50 percent effective at preventing the development of adhesion and do not actively promote healthy healing of tissues.
TTX-333 is the first investigational drug to demonstrate, in a Level 1a double blind randomized controlled trial, clinically meaningful prevention of post-operative adhesions with a 93.3% efficacy rate. (6)
- Many first Is it there or not? – The study rigorously assessed adhesion presence or absence across 23 anatomical sites in the abdomen, evaluating both adhesion from first time surgery and from those who had previous surgery and adhesions were cut during the procedure.
- With reformation rates >90%, absence was still achieved, a first
- Adhesions are end result of a biological process: Mechanistically, TTX-333 distinguishes itself from physical anti-adhesion barriers by systemically modulating fibrotic pathways, thereby preventing adhesions throughout the entire peritoneal cavity rather than at a localized surgical site.
- It can be easily used in laparoscopic procedures, which expands the market, given trends towards minimally invasive and robotic procedures
- Ease of use, with no training or capital equipment investment required by the hospital.
Adhesion Stories
“I am on disability for my adhesions. I am in pain every second of every day…” — Patient.
“This a young otherwise healthy woman, no history or smoking and does not drink, and who has been dealing with severe constipation all her life. She has been working with our motility Clinic. She has been on aggressive bowel regimens including fiber, extensive bowel preparation, and pharmacologic agents to improve her bowel function. These have not really accomplished the goal and the patient is quite dependent upon enemas and pharmacologic agents to have bowel function. This case was substantially more difficult than usual because of lysing adhesions/ scar tissue for 70 minutes.” — Surgeon
Game changer for patients and surgeons:
TTX-333 is the first investigational drug to demonstrate, in a Level 1a double blind randomized controlled trial, clinically meaningful prevention of post-operative adhesions with a 93.3% efficacy rate. (6)
- Attack the fibrosis biology of adhesion formation: TTX-333 distinguishes itself from physical anti-adhesion barriers by systemically modulating fibrotic pathways, thereby preventing adhesions throughout the entire peritoneal cavity rather than at a localized surgical site.
- Flexibility of use: It can be easily used in laparoscopic procedures, which expands the market, given trends towards minimally invasive and robotic procedures
- Ease of use: no training or capital equipment investment required by the hospital.
- Safety: Phase 2 study showed no statistically significant in safety parameters between treatment and control.
Early Access, Compassionate Use, Right to Try
In certain cases, patients are eligible to access experimental drugs while still in clinical development. Every jurisdiction has its own regulations. Learn more
Safer treatments now.
Temple believes postoperative tissue fibrosis is a serious quality-of-life issue, and we seek to address this condition using top-notch science.
Tissue fibrosis is a persistent complication for many patients. At Temple, we are investing millions of dollars into developing solutions for fibrosis, bringing us closer than ever to delivering a new breakthrough to patients.
“Tissue fibrosis causes adhesions which are a big problem, and we would use this drug in every procedure.”
Dr. Rudy Leon De Wilde
TTX333 for safer surgeries.
Temple is developing an impactful product that dramatically reduces tissue fibrosis in patients undergoing abdominal and pelvic surgery.
The drug, TTX333, is easily administered during surgery, both open and laparoscopic, allowing it to act immediately to prevent the formation of adhesions and promote healthy tissue regeneration at the surgical site.
The formation of fibrotic tissue following surgery is a result of the physical trauma and low oxygen levels experienced by cells during the procedure. This disrupts the Krebs cycle, a key process in cellular respiration, which can lead to the development of fibrosis.
Working on the cellular level, our investigative therapy will be the first therapeutic targeting tissue fibrosis and will act throughout the abdominal area with twice the efficacy of existing approaches.
- Ahmad G, Kim K, Thompson M, Agarwal P, O’Flynn H, Hindocha A, et al. Barrier agents for adhesion prevention after gynaecological surgery. Cochrane Database Syst Rev. 2020;3:CD000475. Epub 2020/03/22. doi: 10.1002/14651858.CD000475.pub4. PubMed PMID: 32199406; PubMed Central PMCID: PMC7085418.
- De Wilde RL, Devassy R, Broek RPGT, Miller CE, Adlan A, Aquino P, et al. The Future of Adhesion Prophylaxis Trials in Abdominal Surgery: An Expert Global Consensus. J Clin Med. 2022;11(6). Epub 20220308. doi: 10.3390/jcm11061476. PubMed PMID: 35329802; PubMed Central PMCID: PMC8950418.
- Krielen P, Stommel MWJ, Pargmae P, Bouvy ND, Bakkum EA, Ellis H, et al. Adhesion-related readmissions after open and laparoscopic surgery: a retrospective cohort study (SCAR update). Lancet. 2020;395(10217):33-41. doi: 10.1016/S0140-6736(19)32636-4. PubMed PMID: 31908284.
- Ten Broek RP, Issa Y, van Santbrink EJ, Bouvy ND, Kruitwagen RF, Jeekel J, et al. Burden of adhesions in abdominal and pelvic surgery: systematic review and met-analysis. BMJ. 2013;347:f5588. Epub 2013/10/03. PubMed PMID: 24092941; PubMed Central PMCID: PMC3789584.
- Van den Beukel BAW, Stommel MWJ, van Leuven S, Strik C, IJsseldijk MA, Joosten F, et al. A Shared Decision Approach to Chronic Abdominal Pain Based on Cine-MRI: A Prospective Cohort Study. Am J Gastroenterol. 2018;113(8):1229-37. Epub 2018/06/27. doi: 10.1038/s41395-018-0158-9. PubMed PMID: 29946174.
- Chizen DR, Rislund DC, Robertson LM, Lim HJ, Tulandi T, Gargiulo AR, et al. A randomized double-blind controlled proof-of-concept study of alanyl-glutamine for reduction of post-myomectomy adhesions. Eur J Obstet Gynecol Reprod Biol. 2023;284:180-8. Epub 20230329. doi: 10.1016/j.ejogrb.2023.03.032. PubMed PMID: 37023559.
30%
of patients undergoing abdominal surgery will be readmitted due to an adhesion complication within 10 years.