What changed in this filing

/stocks — the workspaceLOADING

Item 1. Business

2024-03-28 compared with 2023-03-30 · 574 added, 610 removed, 696 unchanged (63% of the section changed)

are a clinical-stage biotechnology company developing regenerative-medicine treatments for disorders of the gastro-intestinal system

and the airway resulting from cancer, trauma or birth defects.

Our technology is based on our proprietary cell-therapy platform that

uses a patient’s own stem cells to regenerate and restore function to damaged organs.

Regenerative Biotech

are a clinical-stage biotechnology company focused on the development of regenerative medicine treatments for disorders of the gastro-intestinal

system and other organs that result from cancer, trauma or birth defects.

Our technology is based on our proprietary cell-therapy platform

that uses a patient’s own stem cells to regenerate and restore function to damaged organs.

We believe that our technology represents

a next generation solution for restoring organ function because it allows the patient to regenerate their own organ, thus eliminating

the need for human donor or animal transplants, the sacrifice of another of the patient’s own organs or permanent artificial implants.

August 2017, we conducted the world’s first successful regeneration of the esophagus after the cancer in the patient’s esophagus

had been surgically removed.

This surgery was performed by Dr.

Dennis Wigle, Chair of Thoracic Surgery at the Mayo Clinic.

were published in the Journal of Thoracic Oncology Clinical and Research Reports in August 2021.

The procedure demonstrated that our

technology was able to successfully regenerate esophageal tissue, including the mucosal lining, to restore the integrity, continuity

and functionality of the esophageal tube.

technology uses mesenchymal stem cells that are retrieved via biopsy from the patient’s abdominal adipose, or fat, tissue prior to surgery.

These stem cells are isolated, expanded and then implanted on a hollow, tubular scaffold made from extremely thin fibers of polyurethane.

The scaffold is then incubated in a customized bioreactor where the stem cells expand further and begin to adhere to the fibers of the

the need for human donor or animal transplants, the sacrificing of another of the patient’s own organs or permanent artificial

technology uses mesenchymal stem cells that are retrieved via biopsy from the patient’s abdominal adipose, or fat, tissue prior

These stem cells are isolated, expanded and then cultured on a tubular scaffold made from extremely thin fibers of polyurethane.

The scaffold is then incubated in a customized bioreactor where the stem cells continue to grow and adhere to the fibers of the scaffold.

The finished graft is then surgically implanted to replace the resected portion of the damaged organ.

Several weeks after surgery,

once a conduit has been established, the implanted scaffold is removed.

No permanent artificial implant remains in the body.

are initially targeting regeneration of the organs of the gastro-intestinal tract and the airway, where organ transplants are not medically

possible today.

Human-donor organ transplants or animal xenotransplants are currently not performed for these organs due to high rates

of rejection.

Additionally, we believe that our technology and intellectual property will allow us to develop organ-regeneration treatments

for other organs.

on our successful first-in-human procedure and our preclinical procedures in over 50 pigs, the U.S.

Food and Drug Administration, or

FDA has approved our Investigational New Drug (IND) application to begin a combined phase 1/2 clinical trial for esophageal

regeneration.

This open-label trial will assess both safety and efficacy in up to ten patients requiring up to a 6cm esophageal

replacement for any reason, including cancer, at up to five U.S.

We have contracted with IQVIA, a leading global provider

of advanced analytics, technology solutions and clinical research services to the life sciences industry, as the contract research

organization (CRO) to manage our first clinical trial.

We intend to initiate this trial in the second quarter of

Our product candidates are currently in development

and have not yet received regulatory approval for sale anywhere in the world.

believe our organ-regeneration technology has the potential for broad applications in the field of medicine, for the repair or replacement

of diseased or damaged organs.

We are initially targeting conditions of the esophagus, including cancer, traumatic injury and birth defects.

Additional product candidates in our development pipeline include ones to treat cancer, injury and birth defects of the bronchus.

on discussions with surgeons familiar with regenerative medicine techniques, we believe that our technology may also be applicable to

treating cancer, injury and birth defects in the colon and intestine.

Several weeks after surgery, once

a conduit has been established, the implanted scaffold is removed using an endoscope.

No permanent artificial implant remains in the

conducted the world’s first successful regeneration of the esophagus in a cancer patient in August 2017.

This surgery was

performed by Dr.

Dennis Wigle, Chair of Thoracic Surgery at the Mayo Clinic in a patient requiring reconstruction of his esophagus

following the removal of a large tumor in his chest.

The results were published in the Journal of Thoracic Oncology Clinical and

Research Reports in August 2021.

The procedure demonstrated that using Harvard Apparatus Regenerative Technology, Inc.’s, or

HRGN’s, technology, we were able to successfully regenerate esophageal tissue, including the mucosal lining, to restore the

integrity, continuity and functionality of the esophageal tube.

Based on our successful first-in-human procedure and our preclinical

procedures in over 50 pigs, the U.S.

Food and Drug Administration, or FDA has approved our Investigational New Drug (IND) application

to begin a phase 1 clinical trial for esophageal regeneration.

This open-label trial will assess both safety and efficacy in up to ten

patients requiring esophageal reconstruction for any reason, including caustic burns, puncture wounds or damage to the esophagus following

chemoradiation therapy for esophageal cancer, at up to five U.S.

We have contracted with IQVIA, a leading global provider of

advanced analytics, technology solutions and clinical research services to the life sciences industry, as the contract research organization

(CRO) to manage our first clinical trial.

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.

We continue to seek our first eligible patient for enrollment in

We are initially targeting regeneration of the organs of the gastro-intestinal

tract and the airway, where organ transplants are not medically possible today.

Human-donor organ transplants or animal xenotransplants

are currently not performed for these organs due to high rates of rejection.

Additionally, we believe that our technology and intellectual

property will allow us to develop organ-regeneration treatments for other organs.

product candidates are currently in development and have not yet received regulatory approval for sale anywhere in the world.

Longevity Products

the second quarter of 2023, our subsidiary in Hong Kong, Harvard Apparatus Regenerative Technology Limited, or Longevity Products, started focusing

on sales of longevity products.

Longevity Products plans to include a

broad range of products focused on personal healthcare including longevity dietary supplements.

The Company started selling longevity

supplements through Longevity Products in the third quarter of 2023.

These products are marketed to the general public and initially targeted at

consumers in the Great China Region through eCommerce (online sales).

We believe our organ-regeneration technology has the potential for

broad applications in the field of medicine, for the repair or replacement of diseased or damaged organs.

We are initially targeting conditions

of the esophagus, including traumatic injury, caustic burns, tissue damage following chemoradiation therapy and birth defects.

product candidates in our development pipeline are targeted at the reconstruction of the colon and uterus wound repair.

strategy is to develop and advance our pipeline of products, beginning with our lead product for the treatment of esophageal cancer,

1 unchanged sentence

The key elements of our strategy include:

phase 1/2 clinical trial for our lead product candidate, the Biostage TM Esophageal Implant, for the treatment of severe

esophageal disease.

Based upon our successful initial case of esophageal regeneration and our animal models, the FDA has approved

our Investigational New Drug (IND) application to commence a clinical trial in up to ten patients.

We plan to initiate this trial

in early 2023.

Advance our other pipeline

products through clinical development.

Based on the establishment of a favorable safety and efficacy profile that we expect to demonstrate

in our phase 1/2 clinical trial for regeneration of the esophagus, we intend to initiate a clinical trial for the treatment of esophageal

atresia, a rare birth defect.

the phase 1 clinical trial for our lead product candidate, the Cellspan TM Esophageal Implant (CEI), for the treatment

of severe esophageal disease.

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.

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.

We continue to

seek our first eligible patient for enrollment in the trial.

our other pipeline products through clinical development.

Based on the establishment of a favorable safety and efficacy profile that

we expect to demonstrate in our phase 1 clinical trial for regeneration of the esophagus, we intend to initiate a clinical trial

for the treatment of esophageal atresia, a rare birth defect where the esophagus does not fully develop, and the affected infant

is unable to swallow food.

As we build our safety and efficacy data, we plan to initiate clinical trials in other areas including

cancer, injury and birth defects in the bronchus.

Develop our technology

for use in other life-threatening conditions that have a relatively shorter time to market.

We believe our technology has broad applications

to treat organ failure.

We intend to develop products focused on life-threatening conditions where current treatments are ineffective,

expensive or both.

Many organ failures are orphan diseases, and we have orphan drug designations from the FDA on our product candidates

for severe disease in both the esophagus and the trachea.

We believe that developing products for such conditions will require smaller

clinical trials and an overall less expensive development pathway than developing treatments for less severe conditions.

Pursue development pathways

in international markets.

In addition to the U.S., we intend to pursue regulatory approval for our products in several key international

markets, including China, Europe and the UK.

Many of the conditions we are targeting have significantly higher patient populations

in foreign countries than in the U.S., thereby making them attractive commercial markets.

We intend to engage foreign health regulatory

bodies to develop clinical and regulatory strategies to gain international approvals.

Collaborate with leading

medical and research institutions to develop our products and build awareness.

We intend to continue to collaborate with thought-leading

medical institutions as we continue clinical development of our products and ultimately reach commercialization.

We currently have

a co-development initiative with the Mayo Clinic and with the Connecticut Children’s Medical Center.

We intend to build additional

partnerships and collaborations with leading institutions that we believe will help to drive awareness of our products and increase

the likelihood of market adoption.

to the American Cancer Society, every year approximately 17,000 Americans are diagnosed with esophageal cancer and approximately 15,000

of these diagnosed patients die from it.

A year after being diagnosed with esophageal cancer, 50% of the patients have died.

years, 80% of these patients have died.

According to the World Health Organization’s International Agency for Research on Cancer,

every year, there are more than 600,000 patients diagnosed with esophageal cancer worldwide.

current treatment for patients with esophageal cancer is removal of the diseased part of the esophagus in a surgical procedure

called an esophagectomy.

The gap left by the removal of part of the esophagus is then repaired using one of two, difficult and

expensive surgeries, both of which have frequent and significant complications.

The first type of surgery is gastric pull-up.

this surgery, the patient’s stomach is reshaped into a tube and pulled up from the abdomen into the chest to connect to the

top of the esophagus.

With gastric pull-up, the patient no longer has a stomach with which to digest food.

In the second type of

surgery, termed colonic interposition, a piece of the patient’s bowel is cut out and used to bridge the gap where the diseased

esophagus was removed.

With colonic interposition, the patient often has insufficient intestine to digest food properly.

surgical procedures have high rates of complications such as damage to the lungs and infections caused by leakage of stomach acids

into the chest.

injury, birth defects and diseases in the colon and other tubular organs that require reconstruction.

our technology for use in other life-threatening conditions that have a relatively short time to market.

We believe our technology

has broad applications to treat organ failure.

We intend to develop products focused on life-threatening conditions where current

treatments are ineffective, expensive or both.

Many organ failures are orphan diseases, and we have orphan drug designations from

the FDA on our product candidates for severe disease in the esophagus.

We believe that developing products for such conditions will

require smaller clinical trials and an overall less expensive development pathway than developing treatments for less severe conditions.

development pathways in international markets.

In addition to the U.S., we intend to pursue regulatory approval for our products

in several key international markets, including China, Europe and the U.K.

Many of the conditions we are targeting have significantly

higher patient populations in foreign countries than in the U.S., thereby making them attractive commercial markets.

engage foreign health regulatory bodies to develop clinical and regulatory strategies to gain international approvals.

we have received Orphan Drug Designation from the European Medicines Agency (EMA) for the use of our CEI for esophageal atresia.

with leading medical and research institutions to develop our products and build awareness.

We intend to continue to collaborate

with thought-leading medical institutions as we continue clinical development of our products and ultimately reach commercialization.

We currently have a co-development initiative with the Mayo Clinic, Connecticut Children’s Medical Center, Yale University

and the McGowan Institute for Regenerative Medicine at the University of Pittsburgh.

We intend to build additional partnerships and

collaborations with leading institutions that we believe will help to drive awareness of our products and increase the likelihood

of market adoption.

According to the American Cancer Society, every year approximately

17,000 Americans are diagnosed with esophageal cancer and approximately 15,000 of these diagnosed patients die from it.

A year after being

diagnosed with esophageal cancer, 50% of patients die.

After five years, 80% of these patients die.

According to the World Health Organization’s

International Agency for Research on Cancer, every year, there are more than 600,000 patients diagnosed with esophageal cancer worldwide.

A current treatment option for patients with esophageal cancer is to

receive neoadjuvant therapy which can include definitive chemoradiation treatment.

In many cases definitive chemoradiation treatment causes

damage to the esophagus leading to severe strictures (constrictions that close the throat and prevent swallowing) or fistulas (holes in

The current treatment for the removal of the diseased part of the esophagus following chemoradiation is to surgically remove

the entire esophagus in a surgical procedure called an esophagectomy.

The gap left by the removal of the diseased part of the esophagus

is then repaired using one of two difficult and expensive surgeries, both of which have frequent and significant complications.

type of surgery is gastric pull-up.

In this surgery, the patient’s stomach is reshaped into a tube and pulled up from the abdomen

into the chest to connect to the top of the esophagus.

With gastric pull-up, the patient no longer has a stomach with which to digest

In the second type of surgery, termed colonic interposition, a piece of the patient’s bowel is cut out and used to bridge

the gap where the diseased esophagus was removed.

With colonic interposition, the patient often has insufficient intestine to digest food

Both surgical procedures have high rates of complications such as damage to the lungs and infections caused by leakage of stomach

acids into the chest.

Even with these surgical treatments, esophageal cancer is one of the deadliest forms of cancer.

3 unchanged sentences

there is an enormous need for, and a huge market for, a better treatment for cancer, injuries, and birth defects of the esophagus.

Solution – Biostage Organ-Regeneration Technology

organ-regeneration technology uses a patient’s own stem cells seeded on a temporary scaffold to regrow and restore their damaged

We believe our technology has numerous advantages over other attempts to restore organ function because our implant is

not a transplant of a human-donor organ, it is not a transplant of an animal organ, it is not a piece of one of the patient’s other

organs, and it is not an artificial implant that remains permanently in the body.

Our implants will allow the patient to regenerate

their own organ inside their own body.

Our esophageal implant consists of a hollow, tubular scaffold consisting of a thin polyurethane fiber mesh that is formed in the shape of the

damaged section of the organ.

This scaffold is seeded with the patient’s own mesenchymal stem cells which are obtained

a few weeks before surgery through a biopsy of adipose (fat) tissue from the patient’s abdomen.

The stem cells are isolated

and expanded and then seeded onto the tubular scaffold.

The scaffold is then be placed into a customized bioreactor for incubation

and further cell expansion.

During several days of incubation in our bioreactor, the stem cells attach to and grow into the

outer 25% of the scaffold.

The stem cell-seeded scaffold is then surgically implanted into the patient to bridge the gap created

where diseased or damaged part of the esophagus was removed.

stem cells then stimulate the body’s natural wound-healing process including stimulating new blood vessel formation,

scar-tissue formation and the remodeling of that scar tissue into esophageal tissue.

The scaffold guides the growth of

new cells to regenerate the esophagus.

After approximately one month, a complete biological tube, or conduit, has formed and after approximately three months, the tube has developed into a layered structure that contains the critical

blood supply, muscles, and mucous-secreting glands to create a functioning esophagus.

At this point, the implanted scaffold is

removed, as it is not a permanent implant.

Solution –Organ-Regeneration Technology

Our organ-regeneration technology uses a patient’s own stem cells

seeded on a temporary scaffold to regrow and restore their damaged organ.

We believe our technology has numerous advantages over other

attempts to restore organ function because our implant is not a transplant of a human-donor or animal organ.

It is also not a piece of

one of the patient’s other organs, and it is not an artificial implant that remains permanently in the body.

Rather, our implants

will allow the patient to regenerate their own organ inside their own body.

esophageal implant consists of a hollow, tubular scaffold consisting of a thin polyurethane fiber mesh that is formed in the shape of

the damaged section of the organ.

This scaffold is then placed into a customized bioreactor and seeded with the patient’s own mesenchymal

stem cells which are obtained a few weeks before surgery through a biopsy of adipose (fat) tissue from the patient’s abdomen.

stem cells are isolated and expanded and then seeded onto the tubular scaffold for incubation and further cell expansion.

During several

days of incubation in our bioreactor, the stem cells attach to and grow into the outer 25% of the scaffold.

The stem cell-seeded scaffold

is then surgically implanted into the patient to bridge the gap created where the diseased or damaged part of the esophagus was removed.

stem cells then stimulate the body’s natural wound-healing process including stimulating new blood vessel formation, scar-tissue

formation and the remodeling of that scar tissue into esophageal tissue.

The scaffold guides the growth of new cells to regenerate the

After approximately one month, a complete biological tube, or conduit, has formed and after approximately three months, the

tube has developed into a layered structure that contains the critical blood supply, muscles, and mucous-secreting glands to create a

functioning esophagus.

At this point, the implanted scaffold is removed, as it is not a permanent implant.

Technology Platform:

How the Biostage Esophageal Implant Works

How the Esophageal Implant Works

bioreactor and scaffold are made in our clean-room facilities in Holliston, Massachusetts and the cell seeding is performed at the FDA-approved,

5 unchanged sentences

These materials are readily available from a variety of suppliers and do not currently represent a large proportion of our total costs.

For our autoseeders and bioreactors, we perform final assembly and testing of components that we buy from third parties like machine

shops, parts distributors, molding facilities and printed circuit board manufacturers.

These manufacturing operations are performed primarily

at our Holliston, Massachusetts headquarters.

of the Biostage Esophageal Implant

with the current standard of care procedures for esophageal cancer patients, either gastric pull-up or colonic interposition, our

esophageal implant offers the following major advantages:

avoid the frequently life-threatening complications of either gastric pull up or colonic interpositioning surgery;

Autologous stem cells eliminate

the risk of immune system rejection;

The procedure does not

require the sacrifice of the patient’s stomach or colon, so those organs remain intact and function accordingly;

It leaves no permanent

implant or artificial structure in the body.

Permanent implants can lead to long-term complications, including infection, which can

lead to further surgical procedures including removal;

Eliminates the need for

sutures where the two ends of the esophagus are joined together.

The sutures are a frequent cause of fluid leaks and infections post-surgery;

Patients can remain on

a reasonable diet after a procedure with our esophageal implant.

For our automatic cell seeding device and bioreactors, we perform final assembly and testing of components that we buy from third parties

like machine shops, parts distributors, molding facilities and printed circuit board manufacturers.

These manufacturing operations are

performed primarily at our Holliston, Massachusetts headquarters.

of the Esophageal Implant

with the current standard of care procedures for esophageal cancer patients - gastric pull-up or colonic interposition, our esophageal

implant offers the following major advantages:

can avoid the frequently life-threatening complications of either gastric pull up or colonic interposition surgery;

stem cells eliminate the risk of immune system rejection;

procedure does not require the sacrifice of the patient’s stomach or colon, so those organs remain intact and function accordingly;

leaves no permanent implant or artificial structure in the body.

Permanent implants can lead to long-term complications, including

infection, which can lead to further surgical procedures including removal;

can remain on a reasonable diet after a procedure with our esophageal implant.

believe that these significant medical advantages will lead to strong demand from patients and doctors for our esophageal implant.

Additionally, we believe that it will receive a favorable reimbursement

profile from payors and insurance companies because of the high cost and complications associated with alternative procedures.

Additionally,

we believe that it will receive a favorable reimbursement profile from payors and insurance companies because of the high cost and complications

associated with alternative procedures.

First-In-Human

Use of the Biostage Esophageal Implant and Scientific Proof of Esophageal Regeneration

August 7, 2017, we announced the use of our esophageal implant in a patient at the Mayo Clinic via an FDA-approved single-use expanded

access, or compassionate use, application.

The patient was a 75-year-old male with a life-threatening cancerous mass in his chest that

spanned his heart, a lung, and his esophagus.

The surgery was performed by Dr.

Dennis Wigle, Chair of Thoracic Surgery, to remove the

tumor, repair the heart, part of one lung, and a section of the esophagus.

Our esophageal implant was interpositioned into the gap in

the esophagus created by the removal of the tumor.

The patient’s surgeon informed us at that time that the surgery was successful,

and the patient was discharged from the hospital 42 days after implantation.

Use of the Esophageal Implant and Scientific Proof of Esophageal Regeneration

On August 7, 2017, we announced the use of our esophageal implant in

a patient at the Mayo Clinic via an FDA-approved single-use expanded access, or compassionate use, application.

The patient was a 75-year-old

male with a life-threatening cancerous mass in his chest that spanned his heart, a lung, and his esophagus.

The surgery was performed

Dennis Wigle, Chair of Thoracic Surgery.

In order to remove the tumor, a portion of the heart was removed and repaired with a pericardial

patch, a portion of the lung was removed, a portion of the vena cava was repaired with a Gortex vascular graft, and a segment of the esophagus

was removed and repaired with our CEI.

The patient’s surgeon informed us at that time that the surgery was successful, and the patient

was discharged from the hospital 42 days after implantation.

The scaffold and stent were removed on day 104 after implantation.

1 unchanged sentence

The surgeon stated

that the cause of death was a stroke, and that the stroke was unrelated to the esophageal implant.

The surgeon also informed us that

a preliminary autopsy had shown that the esophageal implant resulted in a regenerated esophageal tube in the patient, except for a very

small (approximately 5mm) hole outside the implant zone on the lateral wall that was right up against a synthetic graft inserted as part

of the patient’s heart repair on the vena cava in that same surgery.

The synthetic graft on the pericardium was not related to

our esophageal implant product candidate and may have acted as an irritant to esophageal tissue where it contacted the esophageal implant.

The surgeon also informed us that the esophageal regeneration in this patient was consistent with the regeneration previously observed

in our pig studies.

that the cause of death was due to a stroke, and that the stroke was unrelated to the esophageal implant.

The surgeon also informed us

that a preliminary autopsy had shown that the esophageal implant resulted in a regenerated esophageal tube in the patient, except for

a very small (approximately 5mm) hole outside the implant zone.

The small hole was believed to be caused by abrasion from the Gortex

graft used to repair the vena cava.

The surgeon also informed us that the esophageal regeneration in this patient was consistent with

the regeneration previously observed in our pig studies.

results were published in the Journal of Thoracic Oncology Clinical and Research Reports in August 2021.

The photographs below,

taken from the paper, show the explanted esophagus from this procedure.

The photographs below, taken

from the paper, show the explanted esophagus from this procedure.

The image on the left is the actual esophagus.

below, the implant zone is visually almost identical to native esophagus which is the area both above and below the implant zone.

The thickness, color and texture of the regenerated esophagus is nearly indistinguishable from the

native esophagus.

The dark-brown tube in the center of the esophagus

is the stent that was added to avoid narrowing of the esophagus.

The stent for this patient was changed twice, once prior to our esophageal

implant scaffold removal and once after the scaffold and the second stent were removed.

The final stent was removed at five and a half

months post-surgery.

We anticipate that patients treated with our esophageal implant are likely to undergo at least one stent exchange

during their recovery with the discontinuation of stents by six to nine months post-surgery.

Stents are deployed and retrieved endoscopically,

that is, via the mouth, and accordingly, there is no surgical incision in the chest.

images on the righthand side are photographs taken under a microscope to show, from left to right, cells (stained pink), layered

structure (stained blue and purple) and muscles (stained yellow).

The images show a high level of consistency between the

regenerated esophagus and the native esophagus, both to the naked eye and under the microscope.

In the right most panels, the

yellowish coloration along the left side of the images shows a continuous line of muscles running up the regenerated esophagus.

These muscles are the muscularis mucosae which contract to eject mucous into the esophagus.

This mucosal lining is essential to the

long-term survival of the patient because it both lubricates the esophagus to allow food to be swallowed and provides a barrier to

This mucosal lining was seen at three months in both the human patient and in our pig models.

this patient we saw the development of a tube of the patient’s own tissue within one month, and the development of the mucosal

lining within three months.

In pig models we have similarly seen the development of a tube within one month and the development of the

The results from this

study, in combination with previously published results of esophageal regeneration using the CEI tissue-engineered graft 1,2

confirms that the regeneration process is reproducible in humans.

In addition, the data presented confirms that epithelial

regeneration occurs during the initial wave of tissue regeneration and is typically complete by 3 months post-implantation.

La Francesca S, et al (2018).

Long-term regeneration and remodeling of the pig esophagus after circumferential resection using

a retrievable synthetic scaffold carrying autologous cells.

Sundaram, S, et.

Esophageal Regeneration following Surgical Implantation of a Tissue Engineered Esophageal Implant

in a Pediatric Model.

NPJ Regen Med 7:1 .

dark-brown tube in the center of the esophagus is the stent that was added to avoid narrowing of the esophagus.

The stent for this patient

was changed twice, once prior to our esophageal implant scaffold removal and once after the scaffold and the second stent were removed.

The final stent was removed at five and a half months post-surgery.

We anticipate that patients treated with our esophageal implant are

likely to undergo at least one stent exchange during their recovery with the discontinuation of stents by six to nine months post-surgery.

Stents are deployed and retrieved endoscopically, that is, via the mouth, and accordingly, there is no surgical incision in the chest.

images on the righthand side are photographs taken under a microscope to show the characteristics of the newly formed tissue extending

from the native tissue through a transition zone where the regeneration of the muscle layer begins and then into the center of the implant.

The native tissue has multiple layers composed of different cell types, including the mucosal layer on the lumenal surface, a submucosa

composed of connective tissue and smooth muscle cells and the muscular adventitia composed of smooth and striated muscle (brown staining

structures in the right most actin, α-SMA).

In the right most panels, the brown coloration along the left side of the images shows a continuous

line of muscles running up the regenerated esophagus (arrows).

These muscles are the muscularis mucosae which contract to eject mucous

into the esophagus.

This mucosal lining is essential to the long-term survival of the patient because it both lubricates the esophagus

to allow food to be swallowed and provides a barrier to infection.

This mucosal lining was seen at three months in both the human patient

and in our pig models.

this patient we saw the development of a tube comprised of the patient’s own tissue within one month, and the development of the

mucosal lining within three months.

In our clinical trial, the primary endpoint is the development of the tube of the patient’s

tissue within three months and one of the secondary endpoints is the development of the mucosal lining within twelve months.

In pig models we have observed a similar regeneration process with the development of a tube within

one month and the development of the mucosal lining within three months.

In our clinical trial, the primary endpoint is the development

of the tube of the patient’s tissue within three months and one of the secondary endpoints is the development of the mucosal lining

within twelve months.

Models - Pig Studies

pre-clinical animal studies using our esophageal implant investigated several key aspects of the product pertaining to the implant

procedure, cell survival, the architecture of the regenerated tissue at multiple survival time points, the post-implantation

clinical management procedures including Computed Tomography, or CT imaging to assess the growth of new tissue, esophageal stent

management, endoscopy procedures, barium swallow tests and nutritional management.

pre-clinical animal studies using our esophageal implant investigated several key aspects of the product pertaining to the implant procedure,

cell survival, the architecture of the regenerated tissue at multiple survival time points, the post-implantation clinical management

procedures including Computed Tomography, or CT imaging to assess the growth of new tissue, esophageal stent management, endoscopy procedures,

barium swallow tests and nutritional management.

implantation, CT imaging revealed early tissue deposition and the formation of a contiguous tissue conduit.

10 unchanged sentences

image shows an esophagus explanted from a pig 90 days after our esophageal implant was implanted.

The implant zone is visually

almost identical to the native tissue to the left and right of it.

We can note the regeneration of the interior surface of the

esophagus and the regeneration of the surrounding tissue that is visible in red at the top of the red box.

The red color of the

surrounding tissue indicates the presence of a healthy blood supply.

We note further the glossy, reflective coating on the inside of

the esophagus.

This is evidence of the mucosal lining which is essential to the long-term survival of the patient.

lining was seen at three months in the pigs and was also observed in the human patient.

The implant zone is visually almost

identical to the native tissue to the left and right of it.

We note the regeneration of the interior surface of the esophagus and

the regeneration of the surrounding tissue that is visible in red at the top of the red box.

The red color of the surrounding tissue

indicates the presence of a healthy blood supply.

We note further the glossy, reflective coating on the inside of the esophagus.

is evidence of the mucosal lining which is essential to the long-term survival of the patient.

This mucosal lining was seen at three

months in the pigs and was also observed in the human patient.

The investigators concluded that at one year it was difficult to distinguish

1 unchanged sentence

Phase 1 Clinical Trial

on both the successful in-human procedure at the Mayo Clinic and our extensive large-animal research, the FDA has approved our Investigational

New Drug application to commence our clinical trial.

The trial will be a ten-patient combined phase 1/2 trial, in up to five hospitals

that measures both the safety and efficacy of our product candidate in the patient population.

Enrollment criteria includes

any patient that requires removal of a part of the esophagus that is less than six centimeters long for any medical reason.

enrolled patients to include esophageal cancer patients, but we may enroll patients with other esophageal conditions that require regeneration.

We expect to initiate the trial in the second quarter of 2023.

Based on both the successful in-human procedure at the Mayo Clinic

and our extensive large animal research, the FDA has approved our Investigational New Drug application to commence our clinical trial.

The trial will be a ten-patient phase 1 trial, in up to five hospitals in the U.S.

and is designed to measure both the safety and efficacy

of our product candidate in the patient population.

Enrollment criteria includes any patient that requires removal of a part of the esophagus

that is up to six centimeters long for any medical reason.

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.

two clinical trial sites, the Mayo Clinic and the University of Michigan Medical Center, and started screening patients in the third quarter

We continue to seek our first eligible patient for enrollment in the trial.

primary endpoint of the upcoming trial is the establishment of a continuous biological neoconduit, or tube, by three months post-surgery.

8 unchanged sentences

As a result, we believe

that this clinical trial will advance the Biostage Esophageal Implant for numerous indications including to treat esophageal cancer,

Barrett 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.

that this clinical trial will advance the Cellspan Esophageal Implant for numerous indications with the possibility of treating esophageal

damage due to cancer, Barrett’s esophagus, fistulas, traumatic and potentially long-term complications from birth defects in the

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.

January 2022, together with Connecticut Children’s Medical Center, we published in Nature Partner Journals Regenerative Medicine

6 unchanged sentences

Importantly, the piglets also showed normal growth and weight gain which are considered critical in treating human babies.

research also developed novel post-surgical techniques that closely mimic the hospital care that human babies undergo.

These techniques

included non-invasive CT imaging of the regenerated tissue and feeding the piglets via G tubes which are normally used to feed human

babies after surgeries in the gastro-intestinal tract.

research also utilized post-surgical techniques that closely mimic the hospital care that human infants undergo to treat esophageal atresia.

These techniques included non-invasive CT imaging of the regenerated tissue, parenteral feeding via a G tube which are normally used

to feed human infants after surgeries in the gastro-intestinal tract as well as endoscopy using a pediatric endoscope.

believe that this study laid both the scientific and clinical groundwork for treating babies with birth defects in the esophagus with

the Biostage Esophageal Implant.

the Cellspan Esophageal Implant.

The FDA approval for the clinical trial allows us to treat children once we have established safety

in adult patients in the phase 1 clinical trial.

Once we have established the safety of the implant in adults, we expect to recruit

children into the clinical trial.

Once we have established the safety of the implant in adults, we expect to recruit children

into a clinical trial for esophageal atresia.

Drug Designation – Seven Years of Exclusivity

November 2016, we were granted Orphan Drug Designation for our esophageal implant by the FDA to restore the structure and function

of the esophagus subsequent to esophageal damage due to cancer, injury or congenital abnormalities.

We also were granted Orphan Drug

Designation for trachea on September 4, 2014.

November 2016, we were granted Orphan Drug Designation for our esophageal implant by the FDA to restore the structure and function of

the esophagus subsequent to esophageal damage due to cancer, injury or congenital abnormalities.

We also were granted Orphan Drug Designation

for trachea on September 4, 2014.

Orphan Drug Act provides incentives to manufacturers to develop and market drugs and biologics for rare diseases and conditions affecting

5 unchanged sentences

before submitting a new drug application, or NDA, or Biologics License Application or BLA.

After the FDA grants orphan product designation, the identity of the therapeutic

agent and its potential orphan use are disclosed publicly by the FDA.

Orphan product designation does not convey any advantage in or

shorten the duration of the regulatory review and approval process.

The first developer to receive FDA marketing approval for an orphan

biologic is entitled to a seven-year exclusive marketing period in the U.S.

for that product as well as a waiver of the BLA user fee.

The exclusivity prevents FDA approval of another application for the same product for the same indication for a period of seven years,

except in limited circumstances where there is a change in formulation in the original product and the second product has been proven

to be clinically superior to the first.

In addition, Orphan Drug Designation provides a seven-year marketing exclusivity period against

competition in the U.S.

After the FDA grants orphan product designation,

the identity of the therapeutic agent and its potential orphan use are disclosed publicly by the FDA.

Orphan product designation does

not convey any advantage in or shorten the duration of the regulatory review and approval process.

The first developer to receive FDA

marketing approval for an orphan biologic is entitled to a seven-year exclusive marketing period in the U.S.

for that product as well

as a waiver of the BLA user fee.

The exclusivity prevents FDA approval of another application for the same product for the same indication

for a period of seven years, except in limited circumstances where there is a change in formulation in the original product and the second

product has been proven to be clinically superior to the first.

In addition, Orphan Drug Designation provides a seven-year marketing

exclusivity period against competition in the U.S.

from the date of a product’s approval for marketing.

This exclusivity would be in addition to any exclusivity

we may obtain from our patents.

Additionally, orphan designation provides certain incentives, including tax credits and a waiver of the BLA fee.

We also plan to apply for Orphan Drug Designation for our esophageal implant in

Orphan Drug Designation in Europe would provide market exclusivity in Europe for a period of ten years from the date of the product’s

This exclusivity would

be in addition to any exclusivity we may obtain from our patents.

Additionally, orphan designation provides certain incentives, including

tax credits and a waiver of the BLA fee.

We also plan to apply for Orphan Drug Designation for our esophageal implant in Europe.

Drug Designation in Europe would provide market exclusivity in Europe for a period of ten years from the date of the product’s

approval for marketing.

2 unchanged sentences

The key elements of our strategy include:

the phase 1/2 clinical trial for our lead esophageal implant product candidate for the treatment

of severe esophageal disease.

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.

We plan to initiate this trial in the second quarter of 2023.

the phase 1 clinical trial for our lead esophageal implant product candidate for the treatment of severe esophageal disease.

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.

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.

We continue to seek our first eligible patient for enrollment

in the trial.

our other pipeline products through clinical development.

Based on the establishment of a favorable safety and efficacy profile

that we expect to demonstrate in our phase 1/2 clinical trial for regeneration of the esophagus, we intend to initiate a clinical

trial for the treatment of esophageal atresia, a rare birth defect.

As we build our safety and efficacy data, we plan to initiate

clinical trials in other areas including cancer, injury and birth defects in the bronchus.

that we expect to demonstrate in our phase 1 clinical trial for regeneration of the esophagus, we intend to initiate a clinical trial

for the treatment of esophageal atresia, a rare birth defect.

As we build our safety and efficacy data, we plan to initiate clinical

trials in other areas following the demonstration of efficacy in animal models, including colon resection and the prevention of intrauterine

our technology for use in other life-threatening conditions that have a relatively shorter time to market.

3 unchanged sentences

are orphan diseases, and we have orphan drug designations from the FDA on our product candidates for severe disease in both the esophagus

and the trachea.

We believe that developing products for such conditions will require smaller clinical trials and an overall less

expensive development pathway than developing treatments for less severe conditions.

and the colon.

We believe that developing products for such conditions will require smaller clinical trials and an overall less expensive

development pathway than developing treatments for less severe conditions.

development pathways in international markets.

In addition to the U.S., we intend to pursue regulatory approval for our products

in several key international markets, including China, Europe and the UK.

in several key international markets, including China, Europe and the U.K.

Many of the conditions we are targeting, have significantly

9 unchanged sentences

Scaffold Component

proprietary biocompatible scaffold component of our esophageal implant is constructed primarily of extremely thin polyurethane

proprietary biocompatible scaffold component of our esophageal implant is constructed primarily of extremely thin polyurethane fibers.

This material was chosen based on extensive testing of various materials.

The scaffold is made using a manufacturing process

known as electrospinning.

The combination of the electrospinning process, which provides control over the desired microstructure of the

scaffold fabric, with the polyurethane results in a scaffold that we believe has favorable biocompatibility characteristics.

The scaffold is made using a manufacturing process known as

electrospinning.

The combination of the electrospinning process, which provides control over the desired microstructure of the scaffold

fabric, with the polyurethane results in a scaffold that we believe has favorable biocompatibility characteristics.

Patient’s Cells

2 unchanged sentences

a standard biopsy during the weeks leading up to the implant surgery.

Mesenchymal stromal cells are extracted and isolated from the adipose

Mesenchymal stem cells are extracted and isolated from the adipose

tissue biopsy.

3 unchanged sentences

before the implant surgery.

technology is protected by twelve issued U.S.

technology is protected by thirteen issued U.S.

patents (including patents on the bioreactor, the structure of the scaffold and the retrievable

nature of the scaffold), two Orphan-Drug Designations from the FDA, both of which confer seven

years of exclusivity in addition to protection offered by the patents, and our first-mover advantage which allows us to improve the standard

Potential competitors would now have to improve upon our new standard of care rather than just improve on the existing standard

of care in order to get their product candidates approved by the FDA.

In addition, our patent claims cover patches as well as tubular

We intend to develop patches for the repair of tubular organs as well as solid organs.

nature of the scaffold), two Orphan-Drug Designations from the FDA, both of which confer seven years of exclusivity in addition to protection

offered by the patents, and our first-mover advantage which allows us to improve the standard of care.

Potential competitors would now

have to improve upon our new standard of care rather than just improve on the existing standard of care in order to get their product

candidates approved by the FDA.

In addition, our patent claims cover patches as well as tubular structures.

We intend to develop patches

for the repair of tubular organs as well as solid organs.

the “Intellectual Property, Licenses and Related Agreements” section below for more details.

3 unchanged sentences

There are over one million cases of colon cancer.

In addition, there are

approximately 22,000 cases of bronchus cancer that, based on conversations with surgeons, we believe could be treated with our technology.

The following are the approximate case counts by certain geographic region pertaining to the cancers noted below:

Count by Geography

The following are the approximate

case counts by certain geographic region pertaining to the cancers noted below:

Case Count by Geography

Esophagus Adults

Global Cancer Statistics 2020:

5 unchanged sentences

Freddie Bray, BSc, MSc, PhD.

above table excludes case counts for Tracheal Cancer.

We estimate there are approximately 1,000 cases per year of trachea cancer in the

and Europe that are severe enough to be treated with our technology.

Please see “Life-threatening conditions of the Trachea”

These numbers of patients do not include those with fistulas, ulcers, injuries or birth defects, all of which we believe may be

treatable with our technology.

numbers of patients do not include those with fistulas, ulcers, injuries or birth defects, all of which we believe may be treatable with

our technology.

our product candidates are likely to save or extend lives, improve the quality of life, and save money by reducing the complications

7 unchanged sentences

Typically, a year after diagnosis with esophageal

cancer, 50% of the patients are dead and after 5 years, 80% are dead.

cancer, 50% of patients die and after 5 years, 80% die.

are approximately 600,000 new diagnoses of esophageal cancer globally each year, according to the World Health Organization’s International

7 unchanged sentences

the largest potential patient population for our adult esophageal product candidate.

We believe that our esophageal implant,

if approved, has the potential to provide a major advance over the current esophagectomy procedures for addressing esophageal disease,

which have high complication and morbidity rates.

believe that our esophageal implant has the potential to provide physicians a new, simpler procedure to restore organ function

while significantly reducing complication and morbidity rates compared with the current standard of care, and without creating significant

We believe that our esophageal implant, if approved,

has the potential to provide a major advance over the current esophagectomy procedures for addressing esophageal disease, which have

high complication and morbidity rates.

believe that our esophageal implant has the potential to provide physicians a new, simpler procedure to restore organ function while

significantly reducing complication and morbidity rates compared with the current standard of care, and without creating significant

quality of life issues for patients.

Esophageal Atresia

year, it is estimated that approximately 1,000 children in the U.S.

are born with a congenital birth defect known as esophageal atresia.

Esophageal atresia is a condition where an infant is born with an esophagus that does not extend completely from the mouth to the stomach.

When a long segment of the esophagus is lacking, the current standard of care is a series of surgical procedures where sutures are applied

to both ends of the esophagus in an attempt to stretch them and pull them together so they can be surgically connected at a later date.

to the Centers for Disease Control and Prevention (CDC), each year it is estimated that approximately 4,100 children in the U.S.

born with a congenital birth defect known as esophageal atresia.

Esophageal atresia is a condition where an infant is born with an esophagus

that does not extend completely from the mouth to the stomach.

When a long segment of the esophagus is lacking, the current standard

of care is a series of surgical procedures where sutures are applied to both ends of the esophagus in an attempt to stretch them and

pull them together so they can be surgically connected at a later date.

surgical process can take several weeks, and the procedure often involves serious complications and high rates of failure.

7 unchanged sentences

We are working in collaboration with the Connecticut

Children’s Medical Center, to advance an esophageal implant solution to address esophageal atresia that we believe will

be more effective, safer, and less expensive than the current procedures.

Children’s Medical Center, to advance an esophageal implant solution to address esophageal atresia that we believe will be more

effective, safer, and less expensive than the current procedures.

on input from our Scientific Advisory Board, which includes certain well-known surgeons in the field of regenerative medicine, we are

planning to research regenerating other parts of the gastro-intestinal tract such as the stomach, intestine and colon.

planning to research regenerating other parts of the gastro-intestinal tract such as the small intestine and colon.

All these organs

2 unchanged sentences

cancer every year.

(Central Lung) Cancer

cancer is the most common form of cancer and the most common cause of death from cancer worldwide.

There are more than 700,000 new lung

cancer diagnoses annually in the U.S.

In approximately 25% of all lung cancer cases, the cancerous tumor resides only in

a bronchus and not in the lobes of the lungs and is known as central lung cancer.

Approximately 33,000 central lung cancer cases diagnosed

and Europe are Stage I and II and are considered eligible for surgical resection, often with adjuvanted chemotherapy and

Approximately

5,000 of these patients are treated via pneumonectomy, a surgical procedure involving the resection of the cancer tumor, the whole bronchus

below the tumor and the entire lung to which it is connected.

It is a highly complex surgery and due to the removal of a lung, results

in a 50% reduction in the patient’s respiratory capacity.

The procedure has reported rates of post-surgical, or in-hospital, mortality

of 8% to 15%.

Complication rates associated with pneumonectomy are reported as high as 50%, and include post-operative pneumonia, supraventricular

arrhythmias, and anastomotic leakage, placing patients at significant mortality risk post-discharge.

intend to develop a Biostage bronchial implant to treat bronchial cancer, bronchial fistulas (holes), and birth defects in the bronchus.

Based on discussions with surgeons in the field, we estimate that approximately 7,000 of these conditions in the U.S.

and Europe would

be potentially treatable with our technology.

Life-threatening

conditions of the Trachea

are approximately 8,000 patients per year in the U.S.

and Europe who suffer from a condition of the trachea that put the patient at high

risk of death.

These conditions can be due to tracheal trauma, tracheal stenosis or trachea cancer.

There are approximately 40,000 tracheal

trauma patients diagnosed each year in the U.S.

Of those, approximately 1,000 are severe enough to need surgical resection procedures.

Tracheal stenosis is a rare complication from tracheostomies but may have a devastating impact on respiratory function for patients.

Approximately 2,000 patients are diagnosed with stenosis from tracheostomy in the U.S.

Trachea cancer is a very rare but extremely

deadly cancer.

Trachea cancer patients in the U.S.

have a median survival of 10 months from diagnosis and a 5-year survival of only 27%.

There were approximately 200 cases of primary trachea cancer diagnosed in the U.S.

Based on these facts, we estimate that there

are approximately 8,000 patients in the U.S.

and Europe with conditions of the trachea that put them at high risk of death, but for whom

there is currently no clinically effective tracheal implant or replacement method currently available.

believe that a Biostage tracheal implant may provide physicians a treatment to re-establish the structural integrity and function of

a damaged or diseased trachea to address life-threatening conditions due to tracheal trauma, stenosis, cancer, or birth defects.

have not performed regeneration of a trachea using a Biostage tracheal implant.

However, based on the regeneration observed in the bronchus,

we believe that regeneration of the trachea may be possible.

Asherman’s Syndrome is a rare, acquired gynecologic condition

resulting from the buildup of scar tissue and intrauterine adhesions (IUA).

IUA occur primarily after a dilation and curettage (D&C)

procedure for elective termination of pregnancy, a missed or incomplete miscarriage, or to treat a retained placenta after delivery.

can go undetected, but in many cases can lead to altered menstrual cycles (hypomenorrhea) and can ultimately lead to infertility It is

estimated that up to 30% women of reproductive age (15-49 years) in the US that undergo elective pregnancy termination will develop IUA.

Based on the CDC recorded number of elective pregnancy termination of over 600,000 per year 3 , the incidence of Asherman’s

syndrome in the US is estimated to be in excess of 100,000 women in ages 15-49.

We are currently evaluating our technology to prevent

IUA in an animal model of IUA with a prominent laboratory and Chief of Obstetrics and Gynecology.

Data and Statistics - Reproductive Health | CDC

were incorporated under the laws of the State of Delaware on May 3, 2012 as a wholly-owned subsidiary of Harvard Bioscience, Inc., or

5 unchanged sentences

and Harvard Bioscience has not controlled our operations.

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.

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.

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

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.

At that point, we began the second phase of our company’s

1 unchanged sentence

product candidate, the HART-Trachea .

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.

These requirements extended our expectations

regarding our regulatory milestones, and we announced the additional testing and extended milestone expectations in January 2015.

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.

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.

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.

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.

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.

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.

These requirements extended

our expectations regarding our regulatory milestones, and we announced the additional testing and extended milestone expectations in

January 2015.

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.

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.

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

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.

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.

FDA has approved our first clinical trial.

on both the successful human experience at the Mayo Clinic, and our extensive large-animal research (we have performed surgeries on over

50 pigs including for both adult and pediatric diseases), the FDA has approved our clinical trial.

The trial will be a 10-patient combined

phase 1 and phase 2 trial that measures both the safety and efficacy of our product candidate in the patient population.

This clinical

trial is for any patient that requires removal of a part of the esophagus that is less than 6cm long for any reason.

The primary endpoint

in the trial is the establishment of a continuous biological neoconduit, or tube, by three months.

In the human patient, this tube was

seen in one month.

In the pig research, we have seen the formation of a conduit by one month and sometimes by 14 days.

One of the secondary

endpoints will be the development of a mucosal lining in the esophagus by 12 months or earlier.

In the one human patient treated so far,

this mucosal lining was seen at three months.

In the pig research, we have seen this mucosal lining in three months.

FDA approval for our clinical trial allows us to treat babies born without a complete esophagus once we have established safety in adults.

Our esophageal implant will not be tested for safety on healthy volunteers (the usual goal of a phase 1 trial) or for dose-response

and maximum-tolerated dose (the usual goals of a phase 2 trial).

Measuring safety and efficacy in the patient population is normally

the goal of a phase 3 clinical trial.

Hence, our approved trial is more similar to a small phase 3 trial than a typical first clinical

We expect to add patients to this trial, including in Europe and China until we have sufficient data to gain approval.

Based on both the successful human experience at the Mayo Clinic, and

our extensive large-animal research (we have performed surgeries on over 50 pigs including for both adult and pediatric diseases), the

FDA has approved our clinical trial.

The trial will be a 10-patient phase 1 trial that measures both the safety and efficacy of our product

candidate in the patient population.

This clinical trial is for any patient that requires removal of a part of the esophagus that is less

than 6cm long for any reason.

The primary endpoint in the trial is the establishment of a continuous biological neo-conduit, or tube,

by three months.

In the human patient, this tube was seen in one month.

In our pig research, we have seen the formation of a conduit by

one month and sometimes by 14 days.

One of the secondary endpoints will be the development of a mucosal lining in the esophagus by 12

months or earlier.

In the one human patient treated so far, this mucosal lining was seen at three months.

In our pig research, we have

seen this mucosal lining in three months.

a safety profile in our current adult clinical trial will allow us to submit an IND for using our technology to treat esophageal atresia

in the pediatric population.

esophageal implant will not be tested for safety on healthy volunteers (the usual goal of a phase 1 trial) or for dose-response and maximum-tolerated

dose (the usual goals of a phase 2 trial).

Measuring safety and efficacy in the patient population is normally the goal of a phase 3

clinical trial.

Hence, our approved trial is more similar to a small phase 3 clinical trial than a typical first clinical trial.

to add patients to this clinical trial, including in Europe and China until we have sufficient data to gain approval.

the normal drug discovery process, which assesses a drug for its ability to treat a single disease, we can pursue multiple diseases with

1 unchanged sentence

This is because any medical condition that requires the removal of part of the esophagus can be repaired with

the our esophageal implant.

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.

Our esophageal implant can be used to treat any of

these conditions.

Because of this, we believe that the available market in treating the esophagus to be far larger than that for treating

esophageal cancer alone.

In addition, we can access that large patient population without having to conduct a new clinical trial for

each underlying medical condition.

Compared to the development of new drugs, this greatly reduces our costs to expand the market size

for our products.

our esophageal implant.

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.

Our esophageal implant can be used to treat any of these conditions.

this, we believe that the available market in treating the esophagus to be far larger than that for treating esophageal cancer alone.

In addition, we can access that large patient population without having to conduct a new clinical trial for each underlying medical condition.

Compared to the development of new drugs, this greatly reduces our costs to expand the market size for our products.

intend to request Fast Track status, Breakthrough Therapy designation, Regenerative Medicine Advanced Therapy, or RMAT, designation,

2 unchanged sentences

reduced costs and faster times to market.

Please refer the Regulatory Strategy section for more details.

first clinical trial will be in the U.S.

Please refer to the Regulatory Strategy section for more details.

first clinical trial is in the U.S.

for patients with cancer, injury, or birth defects in the esophagus.

However, there are far

more patients with these conditions in Europe and Asia than there are in the U.S.

However, there are far more

patients with these conditions in Europe and Asia than there are in the U.S.

For this reason, we intend to expand our clinical trial

3 unchanged sentences

Conditional approval is country specific but, in general, it would allow us to

market our products, and obtain revenue from the sales of the respective product, after successful phase 2 results.

Conditional approval

is granted subject to the regulatory authority being able to rescind the approval if something goes wrong as more patients get treated.

market our products, and obtain revenue from the sales of the respective product, after successful phase 2 clinical trial results.

Conditional approval is granted subject to the regulatory authority being able to rescind the approval if something goes wrong as

more patients get treated.

Hence, it is possible that we could see revenue in either Asia or the E.U.

before we see revenue in the U.S.

before we see revenue in the

and Development

1 unchanged sentence

materials science, cell biology and engineering.

science, we focus on designing and testing biocompatible organ scaffolds, testing the structural integrity and the cellularization capacities

of the scaffolds.

In cell biology, we focus on developing and testing isolation and expansion protocols, cell characterization and fate

studies, investigating the effects of various cell types and concentrations, evaluating the biocompatibility of scaffolds, experimenting

with different cell seeding methodologies, and developing protocols for implantation experiments.

Our engineering group supports the

materials science and cell biology groups across an array of their activities, i.e.

designing, engineering and making our proprietary

bioreactors and autoseeders.

All three of our R&D groups combine to plan and execute our in vitro studies.

A fundamental part

of our R&D effort in developing our technology has been dedicated to the discovery and development of small and large-animal model

The large-animal model employs the use of Yucatan mini-pigs.

materials science, we focus on designing and testing biocompatible organ scaffolds, testing the structural integrity and the

cellularization capacities of the scaffolds.

In cell biology, we focus on developing and testing isolation and expansion protocols,

cell characterization and cell fate studies, investigating the effects of various cell types and concentrations, evaluating the

biocompatibility of scaffolds, experimenting with different cell seeding methodologies, and developing protocols for implantation

Our engineering group supports the materials science and cell biology groups across an array of their activities, i.e.

designing, engineering and making our proprietary bioreactors and automatic cell seeding device.

All three of our research and

development groups combine to plan and execute our in vitro studies.

A fundamental part of our research and development

effort in developing our technology has been dedicated to the discovery and development of small and large-animal model

addition to our in-house engineering and scientific development team, we collaborate with leaders in the field of regenerative medicine

11 unchanged sentences

have been passed on to our customers.

March 28, 2018, we were awarded a Fast-Track Small Business Innovation Research, or SBIR, grant by the Eunice Kennedy National Institute

of Child Health and Human Development, or NICHD, to support testing of pediatric version of our esophageal implant.

for Phase I provided for the reimbursement of approximately $0.2 million of qualified research and development costs which was received

and recognized as grant income during 2018.

October 26, 2018, we were awarded the Phase II Fast-Track SBIR grant from the Eunice Kennedy NICHD grant aggregating $1.1 million to

support development, testing, and translation to the clinic through September 2019 and represented years one and two of the Phase II

portion of the award.

On August 3, 2020, we were awarded a third year of the Phase II grant totaling $0.5 million for support of development,

testing, and translation to the clinic covering qualified expenses incurred from October 1, 2019 through September 30, 2020.

of 2020, we filed and were granted a one year, no-cost extension for the Phase II grant period extending through September 30, 2021.

the years ended December 31, 2022 and 2021, we recognized $0 and $0.2 million of grant income, respectively, from Phase II of the SBIR

The aggregate SBIR grant to date provided us with a total award of $1.8 million, of which approximately $1.5 million had been

recognized through December 31, 2021.

Phase II portion of the award expired effective September 30, 2021.

research conducted under this grant led to the publication on the regeneration of the esophagus in piglets that was published in January

2022 in collaboration with Connecticut Children’s Medical Center.

Manufacturing

7 unchanged sentences

These materials are readily available from a variety of suppliers and do not currently represent a large proportion of our total costs.

For our autoseeders and bioreactors, we perform final assembly and testing of components that we buy from third parties like machine

shops, parts distributors, molding facilities and printed circuit board manufacturers.

These manufacturing operations are performed primarily

at our Holliston, Massachusetts headquarters.

For our automatic cell-seeding device and bioreactors, we perform final assembly and testing of components that we buy from third parties

like machine shops, parts distributors, molding facilities and printed circuit board manufacturers.

These manufacturing operations are

performed primarily at our Holliston, Massachusetts headquarters.

and Marketing

expect that most surgeries using our esophageal implant will be performed at a relatively small number of major hospitals in

the U.S., Asia and in Europe.

In addition, our technology platform is initially aimed at treating the esophagus, the bronchi, and the

trachea, all of which are treated by thoracic surgeons.

As a result, we expect to employ only a small sales force as compared to companies

selling treatments for larger patient populations.

expect that most surgeries using our esophageal implant will be performed at a relatively small number of major hospitals in the U.S.,

Asia and in Europe.

In addition, our technology platform is initially aimed at treating the esophagus, the bronchi, and the trachea,

all of which are treated by thoracic surgeons.

As a result, we expect to employ only a small sales force as compared to companies selling

treatments for larger patient populations.

expect to price the product commensurate with the medical value created for the patient and the costs avoided with the use of our product.

1 unchanged sentence

with current surgical repair techniques, we expect to charge approximately $250,000 per product in the U.S.

We further expect to be paid by the hospital that

buys the product from us.

Finally, we expect that the hospital would seek reimbursement from government payers, private health insurers

and other third-party payers for the entire transplant procedure, including the use of our products.

further expect to be paid by the hospital that buys the product from us.

Finally, we expect that the hospital would seek reimbursement

from government payers, private health insurers and other third-party payers for the entire transplant procedure, including the use of

our products.

Property, Licenses, and Related Agreements

have twelve issued U.S.

patents that cover the bioreactor, the scaffold, and the surgical procedure.

The patent claims cover the use

of synthetic scaffolds for any use in the gastro-intestinal tract and the airways.

These patents include the claim of having a removable

We have thirteen issued U.S.

patents that cover the bioreactor, the

scaffold, and the surgical procedure.

The patent claims cover the use of synthetic scaffolds for any use in the gastro-intestinal tract

and the airways.

These patents include the claim of having a removable scaffold.

The patent claims cover patches as well as tubes.

We intend to research the patch-based approach to treat damage to solid organs.

We also have two issued patents in China and there are numerous other filings pending.

intend to research the patch-based approach to treat damage to solid organs.

We also have two issued patents in China, one patent issued

in Japan, two patents issued in Europe, two U.S.

orphan-drug designations which can provide seven years of market exclusivity in the U.S.

market after market approval from the FDA and 1 EMA orphan drug designation, which can provide ten years of market exclusivity in the

European market after market approval from the EMA.

There are numerous other filings pending.

We expect these patents to provide protection

4 unchanged sentences

Harvard Bioscience’s right to use the name arises from

a license agreement, effective December 19 th , 2002, between it and the President and Fellows of Harvard University.

Bioscience began at Harvard University in 1903 as Harvard Apparatus and has a license to the name Harvard Apparatus in research and industrial

Our right to use the names in the medical field arises from the sublicense signed when Biostage, Inc.

(then known as Harvard

Apparatus Regenerative Technology) was separated from Harvard Bioscience in 2013 (as more fully described below).

a license agreement, effective December 19, 2002, between it and the President and Fellows of Harvard University.

Harvard Bioscience

delegated its right to use the name in the medical field to us and Harvard Bioscience has no right to use the Harvard mark in the medical

We intend to use this brand name on our products in the future.

We do not have the right to use the Harvard or Harvard Apparatus

marks alone but only as Harvard Apparatus Regenerative Technology.

We believe we are the only licensee of the Harvard name in the medical

products’ field.

This license is perpetual, worldwide and royalty-free.

There are restrictions on our use of the name such as not

using it in the color crimson and not using it in a serifed font.

began at Harvard University in 1903 as Harvard Apparatus and has a license to the name Harvard Apparatus in research and industrial fields.

Our right to use the name in the medical field arises from the sublicense signed when Harvard Apparatus Regenerative Technology was

separated from Harvard Bioscience in 2013 (as more fully described below).

Harvard Bioscience delegated its right to use the name in

the medical field to us and Harvard Bioscience has no right to use the Harvard mark in the medical field.

We intend to use this brand

name on our products in the future.

We do not have the right to use the Harvard or Harvard Apparatus marks alone but only as Harvard

Apparatus Regenerative Technology.

We believe we are the only licensee of the Harvard name in the medical products’ field.

license is perpetual, worldwide and royalty-free.

There are restrictions on our use of the name such as not using it in the color crimson

and not using it in a serifed font.

We currently have no affiliation with Harvard University.

42 unchanged sentences

in the future manufacture, promote and distribute domestically or export internationally are safe and effective for their intended uses:

product design,

preclinical and clinical development and manufacture;

product premarket clearance

and approval;

product safety, testing,

labeling and storage;

recordkeeping procedures;

product marketing, sales

and distribution;

post-marketing surveillance,

complaint handling and adverse event reporting, including reporting of deaths, serious injuries, malfunctions or other deviations;

recall of products, including

repairs or remediation.

design, preclinical and clinical development and manufacture;

premarket clearance and approval;

safety, testing, labeling and storage;

recordkeeping

marketing, sales and distribution;

post-marketing

surveillance, complaint handling and adverse event reporting, including reporting of deaths, serious injuries, malfunctions or other

of products, including repairs or remediation.

labeling, advertising, promotion, marketing and distribution of biologics and medical devices also must be in compliance with the FDA

17 unchanged sentences

Potential FDA enforcement actions include:

untitled letters,

warning letters, fines, injunctions, consent decrees and civil penalties;

unanticipated expenditures

to address or defend such actions

customer notifications

for repair, replacement, refunds;

recall, detention or seizure

of our products;

operating restrictions

or partial suspension or total shutdown of production;

refusing or delaying our

requests for 510(k) clearance or premarket approval of new products or modified products;

operating restrictions;

withdrawing 510(k) clearances

on PMA approvals that have already been granted;

refusal to grant export

approval for our products;

criminal prosecution.

letters, warning letters, fines, injunctions, consent decrees and civil penalties;

unanticipated

expenditures to address or defend such actions

notifications for repair, replacement, refunds;

detention or seizure of our products;

restrictions or partial suspension or total shutdown of production;

or delaying our requests for 510(k) clearance or premarket approval of new products or modified products;

restrictions;

510(k) clearances on PMA approvals that have already been granted;

to grant export approval for our products;

addition, other government authorities influence the success of our business, including the availability of adequate reimbursement from

42 unchanged sentences

have been informed by the FDA that our esophageal implant is a combination biologic/device product.

Biological products must

satisfy the requirements of the PHS Act and the FDCA and their implementing regulations.

The lead reviewing FDA Center will be the Center

for Biologics Evaluation and Research or CBER.

The CBER may choose to consult or collaborate with the FDA’s Center for Devices

and Radiological Health, or CDRH, with respect to the characteristics of the synthetic scaffold component of our product based on the

CBER’s determination of need for such assistance.

Because the CBER is the lead, in order for our esophageal implant to

be legally marketed in the U.S., the product must have a BLA approved by the FDA.

Biological products must satisfy

the requirements of the PHS Act and the FDCA and their implementing regulations.

The lead reviewing FDA Center will be the Center for

Biologics Evaluation and Research or CBER.

The CBER may choose to consult or collaborate with the FDA’s Center for Devices and

Radiological Health, or CDRH, with respect to the characteristics of the synthetic scaffold component of our product based on the CBER’s

determination of need for such assistance.

Because the CBER is the lead, in order for our esophageal implant to be legally marketed in

the U.S., the product must have a BLA approved by the FDA.

discuss both the CBER and the CDRH regulatory paradigms below, as potential future products may implicate elements of each, largely at

244 unchanged sentences

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.

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.

Based on discussions with the FDA, we also expect

clinical trials for our esophageal implant product candidates to be conducted in two sequential phases:

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.

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.

Based on discussions with the FDA, we also expect clinical trials for our esophageal

implant product candidates to be conducted in two sequential phases:

initial trial that combines both phase 1 and phase 2 into a single trial.

2 unchanged sentences

safety and efficacy in a larger patient population.

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

with any clinical trial, clinical testing of our esophageal implant may not be completed successfully within any specified time

period, if at all.

The FDA closely monitors the progress of each phase of clinical trials that are conducted under an IND and may, at

its discretion, reevaluate, alter, suspend, or terminate the testing based upon the data accumulated to that point and the FDA’s

assessment of the risk/benefit ratio to the patient.

The FDA or the sponsor may suspend or terminate clinical trials at any time for

various reasons, including a finding that the subjects or patients are being exposed to an unacceptable health risk.

The FDA can also

request that additional pre-clinical studies or clinical trials be conducted as a condition to product approval.

will submit a BLA once we have sufficient data from the clinical trials to assess the safety and efficacy of our esophageal

We estimate that this process may span a period of three to six years, or longer, considering the uncertainty of a successful

clinical trial.

We anticipate approvals in countries outside of the United States may be shorter, however, we can give no assurance of

such approvals.

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.

with any clinical trial, clinical testing of our esophageal implant may not be completed successfully within any specified time period,

The FDA closely monitors the progress of each phase of clinical trials that are conducted under an IND and may, at its discretion,

reevaluate, alter, suspend, or terminate the testing based upon the data accumulated to that point and the FDA’s assessment of

the risk/benefit ratio to the patient.

The FDA or the sponsor may suspend or terminate clinical trials at any time for various reasons,

including a finding that the subjects or patients are being exposed to an unacceptable health risk.

The FDA can also request that additional

pre-clinical studies or clinical trials be conducted as a condition to product approval.

will submit a BLA once we have sufficient data from the clinical trials to assess the safety and efficacy of our esophageal implant.

We estimate that this process may span a period of three to six years, or longer, considering the uncertainty of a successful clinical

We anticipate approvals in countries outside of the United States may be shorter, however, we can give no assurance of such approvals.

Post-Approval

20 unchanged sentences

Drug Designation

November 2016, we were granted Orphan Drug Designation for our esophageal implant by the FDA to restore the structure and function

of the esophagus subsequent to esophageal damage due to cancer, injury or congenital abnormalities.

We also were granted Orphan Drug

Designation for trachea on September 4, 2014.

November 2016, we were granted Orphan Drug Designation for our esophageal implant by the FDA to restore the structure and function of

the esophagus subsequent to esophageal damage due to cancer, injury or congenital abnormalities.

We also were granted Orphan Drug Designation

for trachea on September 4, 2014.

Orphan Drug Act provides incentives to manufacturers to develop and market drugs and biologics for rare diseases and conditions affecting

22 unchanged sentences

Biologics License Application, or BLA, fee.

We also plan to apply for Orphan Drug Designation for our esophageal implant in

Orphan Drug Designation in Europe would provide market exclusivity in Europe for a period of ten years from the date of the product’s

We also plan to apply for Orphan Drug Designation for our esophageal implant in Europe.

Drug Designation in Europe would provide market exclusivity in Europe for a period of ten years from the date of the product’s

approval for marketing.

25 unchanged sentences

sufficiently profitable not to justify maintenance of market exclusivity.

We intend to apply for orphan drug-designation for our esophageal implant in Europe.

We intend to apply for orphan drug-designation for our esophageal

implant in Europe.

have also formed a subsidiary in Hong Kong, Harvard Apparatus Regenerative Technology Limited, as we continue to assess the market and

7 unchanged sentences

and Human Capital Resources

of December 31, 2022, we had 8 employees working in our business, of whom 7 were full-time and one was part-time.

At that date, all of

our employees were based in the U.S.

of December 31, 2023, our consolidated business employed 18 individuals.

Our employees are located in the U.S.

and Asia and the laws

regarding employee relationships are different by jurisdiction.

None of our employees are unionized.

In general, we consider our relations with our employees to

In general, we consider our

relations with our employees to be good.

Our employees are highly skilled, and many hold advanced degrees.

Our future performance depends significantly upon the continued

service of our key scientific, technical and senior management personnel and our continued ability to attract and retain highly skilled

We have taken proactive steps throughout the COVID-19 pandemic to protect the health and safety of our employees.

to continue to implement these measures until we determine that the COVID-19 pandemic is adequately contained for purposes of our business.

We may take further actions, in compliance with all appropriate government regulations, that we determine to be in the best interest

of our employees.

Our future performance

depends significantly upon the continued service of our key scientific, technical and senior management personnel and our continued

ability to attract and retain highly skilled employees.

We have taken proactive steps throughout the COVID-19 pandemic to protect

the health and safety of our employees.

We expect to continue to implement these measures until we determine that the COVID-19

pandemic is adequately contained for purposes of our business.

We may take further actions, in compliance with all appropriate

government regulations, that we determine to be in the best interest of our employees.

are not aware of any companies whose products are directly competitive with our cell-seeded biocompatible synthetic-scaffold system.

8 unchanged sentences

following table shows information about our executive officers as of March 18, 2024:

Junli (Jerry) He

Executive Officer

2 unchanged sentences

Financial Officer

Junli (Jerry) He – Chairman and Chief Executive Officer

He was appointed as our Chairman and Chief Executive Officer on March 1,

(Jerry) He – Chairman and Chief Executive Officer

He was appointed as our Chairman and Chief Executive Officer (CEO)

on March 1, 2023.

He has served as a member of our Board of Directors since September 1, 2021.

He serves as the Executive Vice Chairman of Bright

Scholar Holdings and has been in that position since January 2019.

He serves as the Executive Vice Chairman

of Bright Scholar Holdings and has been in that position since January 2019.

Prior to the promotion, Mr.

He had served as the CEO of Bright Scholar.

He had served as the CEO of Bright

Prior to joining Bright Scholar, Mr.

He was a Managing Director at Tstone Corp, and served as CFO, CEO and a director of Noah Education

Holdings Ltd., a former NYSE listed private education services provider in China.

He was a portfolio manager at Morgan Stanley Global

Wealth Management from June 2008 to June 2009 and was employed by Bear Stearns from November 2006 to May 2008.

He obtained a bachelor’s

degree in science from Peking University and an M.B.A.

with Honors from the University of Chicago, Booth School of Business.

also a CFA charter holder.

He was a Managing Director at Tstone Corp, and served as Chief Financial Officer, CEO and

a director of Noah Education Holdings Ltd., a former NYSE listed private education services provider in China.

He was a portfolio

manager at Morgan Stanley Global Wealth Management from June 2008 to June 2009 and was employed by Bear Stearns from November 2006 to

He obtained a bachelor’s degree in science from Peking University and an M.B.A.

with Honors from the University of

Chicago, Booth School of Business.

He is also a Certified Financial Analyst (CFA) charter holder.

Yu, BS, MS, CFA – President

Yu has served as our President since May 31, 2018 and has raised over $20 million in capital for Biostage.

Yu is a seasoned executive

with extensive experience in fundraising, strategic analytics, wealth management, and investment research.

Prior to Biostage, Mr.

was a Senior Vice President at Bank of America, where he was employed for nearly 20 years.

Yu has served as our President since May 31, 2018 and has raised over $20 million in capital for Harvard Apparatus Regenerative Technology.

Yu is a seasoned executive with extensive experience in fundraising, strategic analytics, wealth management, and investment research.

Prior to Harvard Apparatus Regenerative Technology, Mr.

Yu was a Senior Vice President at Bank of America, where he was employed for nearly

During his career, Mr.

Yu has developed an

expertise in matching emerging companies with cross-border investors.

Yu holds a B.S.

degree from Peking University (Beijing, China),

Yu has developed an expertise in matching emerging companies with cross-border investors.

degree from Peking University (Beijing, China), and a M.S.

degree from University of Illinois (Chicago, IL).

Yu is a Chartered Financial Analyst.

Yu is a Chartered

Financial Analyst.

William Fodor – Chief Scientific Officer

1 unchanged sentence

On July 2, 2018, Dr.

Fodor became an employee of Biostage after

serving as a consultant to the Company.

Fodor was a founding scientist at Alexion Pharmaceuticals, where he served as an executive

management team member and Senior Director of the Cell/Tissue Engineering, Transgenic Animal and Transplant Programs.

He has also served

as an Associate Professor at the University of Connecticut Department of Molecular Cell Biology and the Center for Regenerative Biology,

extending research areas into cells and cell engineering.

Fodor was Senior Director of Product Development at ViaCell Inc., leading

programs in hematopoietic stem cell process development and manufacturing, mesenchymal stem cell basic research and manufacturing for

cardiac repair and pancreatic stem cell research.

He was a consultant for the biotechnology industry, serving clients in stem cell research,

gene therapy, stem cell manufacturing and stem cell genome engineering.

Fodor has expertise in programs targeting transplant immunology,

hematopoiesis, cardiac repair, stem cell potency, gene therapy for liver diseases, tissue engineering, design and oversight of pre-clinical

non-GLP and GLP animal models and IND Applications (Pre-clinical and CMC Modules).

Fodor became an employee of Harvard Apparatus

Regenerative Technology after serving as a consultant to the Company.

Fodor was a founding scientist at Alexion Pharmaceuticals,

where he served as an executive management team member and Senior Director of the Cell/Tissue Engineering, Transgenic Animal and Transplant

He has also served as an Associate Professor at the University of Connecticut Department of Molecular Cell Biology and the

Center for Regenerative Biology, extending research areas into stem cells and cell engineering.

Fodor was Senior Director of Product

Development at ViaCell Inc., leading programs in hematopoietic stem cell process development and manufacturing, mesenchymal stem cell

basic research and manufacturing for cardiac repair and pancreatic stem cell research.

He was a consultant for the biotechnology industry,

serving clients in stem cell research, gene therapy, stem cell manufacturing and stem cell genome engineering.

Fodor has expertise

in programs targeting transplant immunology, hematopoiesis, cardiac repair, stem cell potency, gene therapy for liver diseases, tissue

engineering, design and oversight of pre-clinical non-Good Laboratory Practices (GLP) and GLP animal models and IND Applications

(Pre-clinical and Chemistry, Manufacturing and Control (CMC) Modules).

Fodor earned a PhD.

In genetics from Ohio State

He completed post-doctoral work at Yale University School of Medicine in the department of immunobiology, investigating the

regulation of MHC class I and MHC class II genes in the histocompatibility complex.

In genetics from Ohio State University.

He completed post-doctoral work at Yale University School of Medicine in the department of immunobiology, investigating the regulation

of Major histocompatibility complex (MHC) class I and MHC class II genes in the histocompatibility complex.

– Chief Financial Officer

11 unchanged sentences

Information and Website

website address is www.biostage.com .

Our Annual Reports on Form 10-K, our Quarterly Reports on Form 10-Q, Current Reports on Form 8-K, and exhibits and amendments

to those reports filed or furnished with the Securities and Exchange Commission, or SEC, pursuant to Section 13(a) of the Exchange Act

are available for review on our website and the SEC website at www.sec.gov.

Any such materials that we file with, or furnish to, the

SEC in the future will be available on our website as soon as reasonably practicable after they are electronically filed with, or furnished

The information on our website is not incorporated by reference into this Annual Report on Form 10-K.

website address is www.hregen.com .

Our Annual Reports on Form 10-K, our Quarterly Reports on Form 10-Q, Current Reports on Form

8-K, and exhibits and amendments to those reports filed or furnished with the Securities and Exchange Commission, or SEC, pursuant to

Section 13(a) of the Exchange Act are available for review on our website and the SEC website at www.sec.gov.

Any such materials that

we file with, or furnish to, the SEC in the future will be available on our website as soon as reasonably practicable after they are

electronically filed with, or furnished to, the SEC.

The information on our website is not incorporated by reference into this Annual

Report on Form 10-K.

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.

What changed 10-K

Item 1. Business