Ownership Profile

MNKD Investors

What exactly is the Technosphere^® Platform?

One of the largest organs in your body are the lungs. Picture the size of a full tennis court and that is roughly the surface area of both lungs in a typical adult. Running through those lungs are airways whose total length measures 1,500 miles – that’s the distance between Chicago and Las Vegas, New York to Albuquerque, and Los Angeles to Nashville.

Simply put, the lungs create a wonderful platform for effective drug delivery. MannKind’s Technosphere technology recognizes this and provides the distinct advantage of rapid, deep lung drug delivery. The effect is similar to intravenous delivery (I.V.; within a vein) and has the added benefit of bypassing the liver which can be especially helpful in reducing systemic side effects.

Examining it closer, it helps to look at inhalation, air flow travel, and the exhale. When you breathe in, air is drawn into the lung and flows down curving, narrowing airways that end in the air sacs or alveoli. When air is exhaled, the flow is reversed. Between the end of an inhalation and the start of exhalation, the air in the lung is stationary. To reach the deep lung, inhaled particles must be carried by the air stream and have enough momentum to continue through the stationary air to collide with the lung surface.

Particles that can reach the lung have aerodynamic diameters between 0.5 µm and 5-6 µm (1 µm is 1 micro-meter or about 0.00004 inches). Particles that are larger than 6 µm will leave the air stream and hit the back of your mouth and throat; smaller than 0.5 µm wouldn’t have the ability to reach the lungs and would simply get exhaled.

“The average Technosphere particle is about 2-2.5 µm which is in the middle of the respirable range,” explains Marshall Grant, PhD, MSc, Executive Director, Clinical Pharmacology & Research for MannKind Corporation. “The particle size distribution is a major reason Technosphere powders are highly efficient in delivering drug to the lungs than other dry powder inhalers (DPIs).”

The Technosphere particles in FDA-approved Afrezza® (insulin human) Inhalation Powder and Tyvaso DPI™ (treprostinil) Inhalation Powder are manufactured by different processes and possess different characteristics. But both are made up of small crystals of FDKP (fumaryl diketopiperazine), MannKind’s proprietary molecule. FDKP provides high solubility and fast dissolution at physiologic pH – and more importantly – can crystallize and form particles in the range appropriate for optimum delivery to the lungs.

When Technosphere powder reaches the lung surface, the FDKP and drug dissolve. The FDKP is then rapidly cleared from the lung into systemic circulation. The FDKP is not metabolized, but rather excreted primarily in the urine. Another value of Technosphere powders has been their versatility – they are compatible with a wide range of doses with different types of drugs.

MannKind’s Technosphere powders are delivered into the lung’s airstream via an inhalation device or DPI (dry powder inhaler). The breath-powered inhalers (Dreamboat® being the most common version) provide excellent delivery efficiency and are proven to deliver up to 70% of the dry-powder dose deep into the lungs. Our DPI are designed to be simple, easy to use and discreet. For patients, imagine having a drug in the convenient form of an inhaler that fits in the palm of your hand. This approach allows patients to not only take control of their health but do it while going about their day and enjoying life more humann.

NTM Lung Disease on the Rise

“I cough every morning upon waking, so I don’t feel rested.” “Imagine not being able to breathe.” “Anxiety ruins everything about you – it’s not a normal life.” “You just exist from day to day and week to week.” These are a sampling of comments about the most bothersome symptoms from living with Nontuberculous Mycobacteria (NTM) shared in a study from NTM Info & Research, Inc. The statements are unfortunately typical and those with NTM often have unpredictable day-to-day health functioning and reduced quality of life.

NTM lung disease is a serious infection that is caused by bacteria that are common in the environment and can cause lung damage. The reality is that we are all exposed to these bacteria in our day-to-day lives – more than 120 species of mycobacteria have been identified. These common bacteria exist in water and soil particles that are in the air, wet places like hot tubs, steamy bathrooms, dishwashers, and even the dewy ground we walk on at the park. But not everyone is at risk of getting NTM lung disease just because they are exposed.

Those predisposed often have underlying conditions such as asthma, COPD, and bronchiectasis, which makes them prone to NTM infection. NTM is not considered to be contagious. Women over the age of 65 make up the majority of those impacted, with a predominance in those of Caucasian and Asian descent.

A rare disease, NTM can often be difficult to diagnose. Many will experience coughing, fatigue, weight loss and shortness of breath – all of which are common with other lung disease symptoms and other conditions like tuberculosis. With NTM, symptoms often worsen, and that is a marker not to be ignored.

It is estimated that some 86,000 individuals are living with NTM lung diseases, and it is on the rise growing 8% each year. Coastal regions including Gulf States have higher rates of infection accounting for 70% of annual NTM cases.

While no cure is available, treatments to manage NTM are available. Treatment for NTM involves antibiotic and multidrug regimens with duration lasting from months to years with tolerability and adverse reactions to treatment which often leads to a lack of adherence to therapy.

There is a valuable need to develop medicines that are well tolerated and effective that lends to consistent patient use and alleviates symptoms of NTM lung disease. MannKind continues to progress MNKD-101 (Clofazimine) for the treatment of NTM.

Institutional Shareholder Rotation

Shareholder	Holders	Value Chg ($MM)	% O/S	Share Change
Buyers	114	74.31	6.77	17,892,432
Sellers	116	-63.33	5.63	-14,883,472
Net		10.98	1.14	3,008,960

Institutional Shareholder Concentration

	Value ($MM)	% O/S	Shares
Total Inst.	618.06	56.91	150,426,949
Top 10 Inst.	374.49	34.56	91,339,773
Top 20 Inst.	466.85	42.98	113,593,587
Top 50 Inst.	563.60	51.87	137,102,477

Institutional Shareholder Style

Style	Holders	Value ($MM)	% Inst Shares	Shares
Growth	51	49.74	4.53	11,982,902
Aggressive Growth	3	2.35	0.22	572,408
Core Growth	36	22.62	2.03	5,368,948
Growth	12	24.77	2.29	6,041,546
Income	7	3.01	0.27	722,242
Income Value	2	2.75	0.25	665,468
Yield	5	0.27	0.02	56,774
Index	28	262.83	24.28	64,174,382
Other	81	236.96	21.86	57,788,169
Broker Dealer	23	42.24	3.90	10,298,073
GARP	17	45.81	4.23	11,174,052
Hedge Fund	40	111.59	10.30	27,216,044
Specialty	--	--	--	--
VC Private Equity	1	37.31	3.44	9,100,000
Value	30	17.96	1.66	4,377,270
Core Value	24	13.60	1.25	3,313,958
Deep Value	6	4.36	0.40	1,063,312

Top Holders: Institutional Investor

Holder	Shares Held	% O/S	Share Change	Filing Date
BlackRock Institutional Trust Company, N.A.	18,370,518	6.95	-230,290	3/31/23
State Street Global Advisors (US)	17,887,348	6.77	628,551	3/31/23
The Vanguard Group, Inc.	13,938,469	5.27	313,563	3/31/23
Avoro Capital Advisors LLC	9,100,000	3.44	--	3/31/23
Fidelity Management & Research Company LLC	6,456,855	2.44	-1,619	3/31/23
D. E. Shaw & Co., L.P.	5,810,053	2.20	207,358	3/31/23
Emerald Advisers LLC	5,514,880	2.09	10,573	3/31/23
Geode Capital Management, L.L.C.	5,157,086	1.95	241,070	3/31/23
Two Sigma Investments, LP	5,119,882	1.94	3,389,178	3/31/23
Millennium Management LLC	3,984,682	1.51	-2,265,257	3/31/23
Nuveen LLC	3,574,020	1.35	2,784,563	3/31/23
BofA Global Research (US)	2,838,103	1.07	1,475,480	3/31/23
Citadel Advisors LLC	2,797,149	1.06	-1,352,553	3/31/23
Castagna (Michael E)	2,529,723	0.96	496,607	5/26/23
Northern Trust Investments, Inc.	2,078,408	0.79	-30,261	3/31/23
Charles Schwab Investment Management, Inc.	1,930,382	0.73	3,705	3/31/23
Woodline Partners LP	1,834,280	0.69	1,113,420	3/31/23
Lazard Asset Management, L.L.C.	1,715,013	0.65	246,549	3/31/23
180 Wealth Advisors, L.L.C.	1,482,638	0.56	14,491	3/31/23
Parkman Healthcare Partners LLC	1,474,098	0.56	442,989	3/31/23
Principal Funds, Inc.	1,441,566	0.55	-5,565	4/30/22
Rafferty Asset Management LLC	1,382,870	0.52	100,673	3/31/23
Goldman Sachs & Company, Inc.	1,307,748	0.49	390,900	3/31/23
Renaissance Technologies LLC	1,171,345	0.44	-774,100	3/31/23
Citi Investment Research (US)	1,108,586	0.42	542,155	3/31/23
Tross Stuart A	1,036,329	0.39	208,280	5/25/23
Apollo Capital Management, L.P.	964,113	0.36	629,887	3/31/23
Thomson (David B)	960,424	0.36	101,228	5/25/23
Susquehanna International Group, LLP	866,811	0.33	-54,832	3/31/23
Schonfeld Strategic Advisors LLC	847,014	0.32	-2,015,886	3/31/23
Binder (Steven B)	845,819	0.32	214,852	5/25/23
Kocinsky (Joseph)	827,832	0.31	-110,538	3/23/23
Voya Investment Management LLC	816,322	0.31	35,078	3/31/23
Morgan Stanley & Co. LLC	809,445	0.31	4,581	3/31/23
BlackRock Financial Management, Inc.	791,484	0.30	30,279	3/31/23
BNP Paribas Securities Corp. North America	745,414	0.28	476,135	3/31/23
BlackRock Investment Management, LLC	741,014	0.28	-44,906	3/31/23
Scopia Capital Management LP	694,961	0.26	--	3/31/23
Raymond James & Associates, Inc.	654,961	0.25	35,694	3/31/23
BNY Mellon Asset Management	649,844	0.25	-5,208	3/31/23
Barclays Bank PLC	558,652	0.21	-147,236	3/31/23
ExodusPoint Capital Management, LP	539,986	0.20	295,953	3/31/23
Schweizerische Nationalbank	539,700	0.20	-50,600	3/31/23
1492 Capital Management, LLC	536,725	0.20	-1,105	3/31/23
UBS Financial Services, Inc.	535,572	0.20	-365,822	3/31/23
Morgan Stanley Smith Barney LLC	456,507	0.17	-26,378	3/31/23
Cubist Systematic Strategies, LLC	440,293	0.17	78,637	3/31/23
EAM Investors, LLC	436,482	0.17	436,482	12/31/22
Rhumbline Advisers Ltd. Partnership	411,929	0.16	16,232	3/31/23
UBS Asset Management (Americas), Inc.	389,142	0.15	-9,868	3/31/23

* Insider values reflect direct beneficial ownership.