19 unchanged sentences
We activated two clinical trial sites, the Mayo Clinic and the University of Michigan Medical Center, and started screening patients in the third quarter of 2023.
+Added: We activated a clinical trial site at the University of Southern California in Los Angeles, and started screening patients in the first quarter of 2026.
We continue to seek our first eligible patient for enrollment in the trial.
10 unchanged sentences
Consumer Health Products
−Removed: In the second quarter of 2023, our subsidiary in Hong Kong, Harvard Apparatus Regenerative Technology Limited, or Consumer Health Products, started focusing on sales of consumer health products (formerly identified as “longevity products”).
+Added: Our subsidiary in Hong Kong, Harvard Apparatus Regenerative Technology Limited, or Consumer Health Products, focuses on sales of consumer health products (formerly identified as “longevity products”).
Consumer Health Products plans to include a broad range of products focused on personal healthcare including dietary supplements.
−Removed: The Company started selling consumer health supplements through Consumer Health Products in the third quarter of 2023.
These products are commercially marketed to the general public and initially targeted at consumers in Asia through eCommerce (online sales).
7 unchanged sentences
Based upon our successful initial case of esophageal regeneration and our animal models, the FDA has approved our IND application to commence a clinical trial in up to ten patients.
−Removed: We activated two clinical trial sites, the Mayo Clinic and the University of Michigan Medical Center, and started screening patients in the third quarter of 2023.
+Added: We activated three clinical trial sites, the Mayo Clinic, the University of Michigan Medical Center and the University of Southern California in Los Angeles.
We continue to seek our first eligible patient for enrollment in the trial.
125 unchanged sentences
We expect enrolled patients to include esophageal cancer patients, post-neoadjuvant chemoradiation therapy, but we may enroll patients with other esophageal conditions that require reconstruction and regeneration.
−Removed: We activated two clinical trial sites, the Mayo Clinic and the University of Michigan Medical Center, and started screening patients in the third quarter of 2023.
+Added: We activated three clinical trial sites, the Mayo Clinic, the University of Michigan Medical Center and the University of Southern California in Los Angeles.
We continue to seek our first eligible patient for enrollment in the trial.
20 unchanged sentences
Once we have established the safety of the implant in adults, we expect to recruit children into a clinical trial for esophageal atresia.
+Added: We are collaborating with the Capital Medical University in China to advance an investigator-initiated trial (IIT) focused on esophageal atresia.
+Added: Data generated from this clinical work may be used to support our development strategy, including potentially serving as supplemental or bridging information in future regulatory submissions to the U.S.
+Added: Food and Drug Administration (FDA).
+Added: We cannot assure that data derived from the IIT will be accepted by the FDA or that such data will be sufficient to support any regulatory approval.
+Added: The timing, scope, and outcome of regulatory interactions remain subject to FDA review and discretion.
Orphan Drug Designation – Seven Years of Exclusivity
21 unchanged sentences
Based upon our successful initial case of esophageal regeneration and our animal models, the FDA has approved our IND application to commence a clinical trial in up to ten patients.
−Removed: We activated two clinical trial sites, the Mayo Clinic and the University of Michigan Medical Center, and started screening patients in the third quarter of 2023.
+Added: We activated three clinical trial sites, the Mayo Clinic, the University of Michigan Medical Center and the University of Southern California in Los Angeles.
We continue to seek our first eligible patient for enrollment in the trial.
68 unchanged sentences
Since the Separation we have been a separately traded public company and Harvard Bioscience has not controlled our operations.
−Removed: Following the Separation, we continued to innovate our bioreactors based on our physiology expertise, we developed our materials science capabilities and we investigated and developed a synthetic tracheal scaffold.
−Removed: By that time, we had built and staffed cell biology laboratories at our Holliston facility, to give ourselves the ability to perform and control our scientific investigation and developments internally.
−Removed: At that point, we began the second phase of our company’s development.
−Removed: In mid-2014, we increased the pace of our scientifically based internal analysis and development of our first-generation tracheal implant product candidate, the HART-Trachea .
−Removed: From large-animal studies conducted thereafter we found that the product candidate elicited an unfavorable inflammatory response after implantation, which required additional development and testing.
−Removed: These requirements extended our expectations regarding our regulatory milestones, and we announced the additional testing and extended milestone expectations in January 2015.
−Removed: During 2015 we isolated and tested all major variables of the organ scaffold and the cell source and protocols, examining the effects of alternatives against the then-existing product approach.
−Removed: Through extensive in vitro preclinical studies, and small-animal and large-animal studies, we made dramatic improvements, and discovered that the mechanism of action of our current approach was very different from our hypothesis regarding that of the first-generation product candidate.
−Removed: Our technology uses a different scaffold material and microstructure, a different source and concentration of the patient’s cells and several other changes from our earlier trachea initiative.
−Removed: These changes resulted in a scaffold that was temporary and could be removed via the mouth in an endoscopic procedure that did not require major surgery in the chest.
−Removed: The temporary nature of the scaffold reduces the risk of long-term complications that can arise from permanent implants such as those from hernia meshes and breast implants.
CLINICAL TRIALS
14 unchanged sentences
Hence, our approved trial is more similar to a small phase 3 clinical trial than a typical first clinical trial.
−Removed: We expect to add patients to this clinical trial, including in Europe and China until we have sufficient data to gain approval.
+Added: We do not expect to add patients to this clinical trial, including in Europe and China, until we have sufficient data to gain approval.
Unlike the normal drug discovery process, which assesses a drug for its ability to treat a single disease, we can pursue multiple diseases with a single clinical trial.
This is because any medical condition that requires the removal of part of the esophagus can be repaired with our esophageal implant.
−Removed: It does not matter that the need to surgically remove part of the esophagus is caused by esophageal cancer, Barrett esophagus (damage to the lower esophagus caused by the reflux of stomach acids into the esophagus), a fistula (a hole in the esophagus), a birth defect, or a wound or injury to the esophagus.
+Added: It does not matter that the need to surgically remove part of the esophagus is caused by esophageal cancer, Barrett's esophagus (damage to the lower esophagus caused by the reflux of stomach acids into the esophagus), a fistula (a hole in the esophagus), a birth defect, or a wound or injury to the esophagus.
Our esophageal implant can be used to treat any of these conditions.
9 unchanged sentences
For this reason, we intend to expand our clinical trial to include patients in Europe and Asia and to seek regulatory approval in those countries as well.
+Added: We are actively collaborating with the Capital Medical University in China to advance an investigator-initiated trial (IIT) for the treatment of esophageal atresia.
+Added: This collaboration is intended to further assess the clinical feasibility and potential therapeutic benefit of our technology.
+Added: Data generated from the IIT may contribute to our overall development strategy and may be considered as supplemental information in connection with future regulatory interactions, including potential submissions to the U.S.
+Added: Food and Drug Administration (FDA).
+Added: We cannot provide assurance regarding the acceptability of such data by the FDA or the extent to which the IIT results may support regulatory approval.
+Added: Our clinical development activities, regulatory timelines, and related expenditures remain subject to inherent risks and uncertainties.
In addition to having large patient populations, for product candidates like ours, both the European Union, or E.U., and some countries in Asia allow for “conditional approval”.
82 unchanged sentences
(1) complying with cGMP for each constituent part, or (2) a streamlined approach specific to combination products, subject to certain limitations.
+Added: Regenerative biotechnology products in the People’s Republic of China (“PRC”), including cell therapy and tissue-engineered products, are regulated by the National Medical Products Administration (“NMPA”) under regulatory frameworks that continue to evolve.
+Added: Depending on product characteristics, candidates may be subject to regulatory pathways applicable to biologics, drugs, medical devices, or combination products, which influence applicable preclinical, clinical, manufacturing, and approval requirements.
+Added: Product development typically involves regulatory authorization to conduct clinical studies, compliance with applicable quality and good manufacturing practice (“GMP”) standards, and submission for marketing approval.
+Added: Regulatory classification, data requirements, and approval processes are complex and subject to regulatory interpretation.
Regulatory Strategy
177 unchanged sentences
Based on the FDA’s approval of our clinical trial for any condition that requires removal of part of the esophagus, we believe that we are able to pursue the treatment of multiple diseases, injuries or birth defects with a single clinical trial.
−Removed: As a result, we believe that this clinical trial will advance our esophageal implant for numerous indications including to treat esophageal cancer, Barrett esophagus, fistulas, traumatic injury to the esophagus and birth defects in the esophagus.
+Added: As a result, we believe that this clinical trial will advance our esophageal implant for numerous indications including to treat esophageal cancer, Barrett's esophagus, fistulas, traumatic injury to the esophagus and birth defects in the esophagus.
Compared to developing treatments for a single underlying medical condition, we believe that addressing multiple medical conditions in a single clinical trial has the potential to significantly reduce our costs to expand the market for our products.
3 unchanged sentences
If successful, the initial trial would be followed by a phase 2 Registration, or Pivotal Trial, to test the product candidate’s safety and efficacy in a larger patient population.
−Removed: We believe that the nature of the our esophageal implant and the sizes of their targeted patient populations would lead to a small number of patients in this trial, relative to most biotechnology clinical trials.
+Added: We believe that the nature of our esophageal implant and the sizes of its targeted patient populations would lead to a small number of patients in this trial, relative to most biotechnology clinical trials.
As with any clinical trial, clinical testing of our esophageal implant may not be completed successfully within any specified time period, if at all.
140 unchanged sentences
Compared sentence by sentence after normalising whitespace, quotation marks, case and digits, so re-formatting and restated figures do not read as changed language. Wording changes appear as one removal and one addition. The current filing and the prior one are authoritative.