Learn about Kringle Pharma

Quick Guide to Kringle and HGF

Who is Kringle Pharma?

Corporate Philosophy
We will contribute to the society and global health by research,
development and commercialization of innovative medicines for patients suffering from incurable diseases.

We focus our managerial resources on development of recombinant human HGF protein, in the belief that it will lead to therapeutic innovation, creating business opportunities and maximizing the value of the company.
To ensure the outcomes of its development are commercialized into pharmaceuticals that contribute meaningfully to society, our basic policy is to secure marketing approval on our own through in-house development primarily in Japan.

Kringle Pharma is a biopharmaceutical biotech focused on the development of HGF medicine

Established in
2001
Clinical-stage pipelines
4
(2 programs in Phase III)
Patents
28
(including 3 patent applications, as of January 2023)
R&D expenses
710 million yen
(ending September 2023)
Equity ratio
76.6% （As of September 30, 2023）

Kringle Pharma is a biopharmaceutical company founded as a biotech startup based on the research findings at Osaka University and Keio University. We are the only company in the world who have capability to mass-produce GMP-compliant, pharmaceutical-grade HGF (hepatocyte growth factor) for clinical use and have multiple clinical-stage pipelines. We aim to provide novel HGF therapies to the world for patients suffering from intractable diseases for which there is no truly effective treatment.

What is HGF?

Originally discovered in Japan, HGF is a protein in human body that regenerates the liver

It has long been known that the liver has a strong regenerative capacity. For example, even if two-thirds of the human liver is removed, it eventually regenerates to its original size in about one month.
In 1984, HGF (hepatocyte growth factor) was identified by the late Professor Emeritus Toshikazu Nakamura of Osaka University as the principal factor contributing to the liver regeneration.

HGF protects, regenerates and repairs tissues and organs

HGF, discovered by Professor Nakamura, was later found to play a key role in the regeneration and repair of not only the liver but also various other organs and tissues and has a powerful effect on the nervous system.
On animal disease models, recombinant human HGF protein or HGF expression vectors have demonstrated the effectiveness in the prevention or treatment of a range of diseases for which no effective treatments were available, These included acute diseases (e.g. spinal cord injury, fulminant hepatitis, acute kidney injury, and myocardial infarction) as well as chronic diseases (e.g. cirrhosis, chronic kidney disease, pulmonary fibrosis, dilated cardiomyopathy, Huntington’s disease, and amyotrophic lateral sclerosis).

Diseases with potential clinical application of recombinant human HGF protein

HGF(hepatocyte growth factor)
  • Kidney
    Acute kidney injury, chronic renal failure, renal transplantation, diabetic nephropathy
  • Liver
    Acute hepatitis, fulminant hepatitis, liver cirrhosis, biliary atresia, fatty liver, liver transplantation
  • Heart and blood vessels
    Vascular disease (arteriosclerosis obliterans, vascular restenosis prevention, etc.), myocardial infarction, dilated cardiomyopathy
  • Nervous system
    ALS, acute phase spinal cord injury, cerebral infarction, Parkinson’s disease, Huntington’s disease, dementia
  • Lungs and bronchi
    Chronic obstructive pulmonary disease (COPD), pulmonary fibrosis, bronchial asthma
  • Others
    Skin ulcer,vocal fold scar, inflammatory bowel disease, corneal injury

*Red text indicate target diseases for which we are currently developing drugs

Kringle Pharma named after HGF’s “Kringle” structure

An HGF protein has a complex molecular structure consisting of 692 linked amino acids. The molecule has four “Kringle” structures. A “Kringle” is a characteristic structure that resembles the kringle, a traditional Danish pastry.
Kringle Pharma is named after this “Kringle” structure, combined with “Pharma” to indicate it is a pharmaceutical company.

Development Pipeline

We have four pipelines that have progressed to clinical trials: acute phase spinal cord injury, vocal fold scar, ALS, and acute kidney injury. Phase III studies, the final stage of clinical trials, are underway in acute phase spinal cord injury and vocal fold scar. Claris Biotherapeutics, Inc. our partner in the US, is conducting a clinical trial in the US and Canada for ophthalmic diseases. In addition, we have several pipelines in the basic research stage. Currently, we are focusing our resources on drug development for acute phase spinal cord injury, which is at the most advanced stage of development, to obtain manufacturing and marketing approval. Meanwhile, for basic research, we are actively conducting joint research projects with universities and other institutions to expand indications and search for new seeds.

Now Kringle Pharma develops drugs for:

Acute Spinal Cord Injury（Acute SCI）

Vocal fold scar

ALS

Acute kidney injury

Diseases for joint research

Ophthalmic diseases

Other neurological diseases

Exploratory stage

Pipeline development status

Target disease Development stage Basic research Non-clinical study Clinical study Application/approval Commercial
Phase I Phase II Phase III
Acute Spinal Cord Injury
（Acute SCI）		 Phase I/II study (placebo-controlled double-blind comparative study) completed, POC obtained, orphan drug designation obtained, Phase III study completed Completed Completed
Vocal fold scar Phase I/II study (open-labelled dose-escalating investigator-initiated study) completed, Phase III study (placebo-controlled double-blind comparative study) ongoing Completed Ongoing
ALS Phase II study (placebo-controlled double-blind comparative investigator-initiated study) completed, no statistically significant difference in primary and secondary endpoints, Additional analyses ongoing. Completed Completed
Acute kidney injury Phase Ia and Ib (single and repeated dosing study) completed in the U.S. -Searching for a partner Completed Searching for a partner
Ophthalmic diseases Development by Claris Biotherapeutics in the US (HGF supplied by Kringle Pharma)
Phase I/II study in progress 		Completed Ongoing
Other neurological diseases Joint research with Keio University Ongoing
Exploratory stage Joint researches with Kanazawa University, Kyoto University, etc Ongoing

* LPO : Last Patient Out
** FPI : First Patient In

As of Nov 2023

Please click below for more information about our research and development.

Research & Development

HGF Potentials

Potential market size

The numbers of patients are limited as they are patients with acute phase spinal cord injury, vocal fold scar, and ALS, which are rare diseases. However, biopharmaceutical products like HGF are generally priced higher compared to small molecule products. HGF medicine is likely to be used widely once launched because there are few competitive products for those rare diseases, Accordingly, the market size of HGF worldwide is expected to reach tens of billions of yen for a single target indication.

Target disease Number of patients*1 Competitor products HGF market size*3
Japan World total*2
Neurological diseases Acute Spinal Cord Injury （Acute SCI） 5,000 60,000 Stemirac, cell therapy, etc.
* Combination with HGF considered
Japan：
Up to 10 billion yen
Overseas：
Up to 50 billion yen
ALS 9,800 85,000 Riluzole, Edaravone, etc.
* Combination with HGF considered
Japan：
Up to 20 billion yen
Overseas：
Up to 100 billion yen
Fibrosis diseases Vocal fold scar 12,000 100,000 Laryngoplasty, etc. (limited effect)
* HGF will be the only drug therapy
Japan：
Up to 5 billion yen
Up to 5 billion yen：
Up to 30 billion yen
  • *1 Sources:
    Our estimates based on Medscape Reference HP, Japan Intractable Diseases Information Center HP, The National Spinal Cord Injury Association HP, DATAMONITOR report, ASAKURA Internal Medicine 10th edition, published papers, etc., and “World Population Trends” by Statistics Bureau, Ministry of Internal Affairs and Communications
  • *2
    Developed countries where advanced treatment is available
  • *3
    Our forecast: calculated based on expected number of patients, diagnosis rate, treatment rate, drug utilization rate, and drug prices

Expansion from acute injury phase to chronic injury phase of spinal cord injury

Through collaborative research with the Keio University School of Medicine, we aim to develop new therapies not only for the acute phase, but also for the subacute and the chronic phase of spinal cord injury. Expanding the indication to the chronic phase, the target number of the patients will significantly increase, and it will enlarge the market by at least 20 times.

  • 1)
    Hikosuke Shingu, Prevention of Spinal Cord Injury, Journal of the Japan Medical Society of Paraplegia 13:48-49, 2000
  • 2)
    Hiroaki Sakai, Survey for spinal cord injuries in Fukuoka. Sogo rehabilitation 36: 969–972, 2008
  • 3)
    Developed countries where advanced treatment is available
  • 4)
    Company estimates based on the number of patients in Japan, Spinal Cord Injury Facts and Figures at a Glance (2021), and Global Population Trends by the Statistics Bureau of the Ministry of Internal Affairs and Communications (MIC)
  • 5)
    Company estimates based on Spinal Cord Injury Facts and Figures at a Glance (2021), The International Spinal Cord Injury Society Website, and Global Population Trends by the Statistics Bureau of the MIC

Expansion from vocal fold scar to other fibrosis diseases

If we are able to bring an HGF medicine to the world in vocal fold scar, we believe this will pave the way for a wider application of HGF to other chronic diseases caused by fibrosis. These fibrosis diseases have a larger number of patients and there are huge market needs and potentials.

  • *1
    Calculated based on prevalence in Japan
  • *2
    GBD 2015 Disease and Injury Incidence and Prevalence Collaborators. Global, regional, and national incidence, prevalence, and years lived with disability for 310 diseases and injuries, 1990–2015: a systematic analysis for the Global Burden of Disease Study 2015. Lancet 2016; 388: 545-602.

Future of Kringle Pharma

On top of the pipeline in neurological diseases (acute phase spinal cord injury and ALS), Kringle Pharma will promote development in fibrosis diseases (vocal fold scar) to better serve patients and maximize the long-term business value.

Our desire is, to provide innovative HGF medicines as soon as possible to bring smiles to patients and their families.